1.Crosstalk Between the Nervous System and Colorectal Cancer.
Xi LI ; Chunshui YE ; Min WANG ; Patrick KWAN ; Xin TIAN ; Yanke ZHANG
Neuroscience Bulletin 2025;41(1):93-106
The nervous system is the dominant regulatory system in the human body. The traditional theory is that tumors lack innervation. However, an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system. Globally, colorectal cancer (CRC) is the third most common cancer. With the rise of tumor neuroscience, the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention. However, there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC. This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC, focusing on the following areas: (1) Effects of the nervous system on colon cancer. (2) Effects of CRC on the nervous system. (3) Treatment of CRC associated with the nervous system.
Humans
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Colorectal Neoplasms/therapy*
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Animals
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Nervous System/metabolism*
2.Characteristics of traditional Chinese medicine syndromes in patients with Chikungunya hemorrhagic fever:a cross-sectional study
Shiying LU ; Danwen ZHENG ; Xintian HONG ; Yuping LIU ; Guangzong LI ; Zhifeng HONG ; Jinghua YANG ; Yan ZHANG ; Banghan DING ; Yuntao LIU ; Yuanyuan WANG ; Xin YIN ; Jingwei SHUI ; Xiaofei FAN ; Hai LAN ; Zhongde ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(11):1531-1539
Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.
3.Xiaozhen Fang alleviates erlotinib-induced skin toxicity in mice by in-hibiting pyroptosis via NLRP3/caspase-1/GSDMD signaling pathway
Xintian WANG ; Cheng CHENG ; Ling LUO ; Yan CHEN ; Yuping LIU ; Haiyan XING
Chinese Journal of Pathophysiology 2025;41(7):1392-1399
AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.
4.Xiaozhen Fang alleviates erlotinib-induced skin toxicity in mice by in-hibiting pyroptosis via NLRP3/caspase-1/GSDMD signaling pathway
Xintian WANG ; Cheng CHENG ; Ling LUO ; Yan CHEN ; Yuping LIU ; Haiyan XING
Chinese Journal of Pathophysiology 2025;41(7):1392-1399
AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.
5.Characteristics of traditional Chinese medicine syndromes in patients with Chikungunya hemorrhagic fever:a cross-sectional study
Shiying LU ; Danwen ZHENG ; Xintian HONG ; Yuping LIU ; Guangzong LI ; Zhifeng HONG ; Jinghua YANG ; Yan ZHANG ; Banghan DING ; Yuntao LIU ; Yuanyuan WANG ; Xin YIN ; Jingwei SHUI ; Xiaofei FAN ; Hai LAN ; Zhongde ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(11):1531-1539
Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.
6.Establishment of a standardized daily behavior collection and analysis system for brain disease models of rhesus and cynomolgus monkeys and its application in autism spectrum disorder.
Xiaofeng REN ; Huimin WANG ; Xiaoman LV ; Yi ZHOU ; Yingyin FAN ; Yanjun YU ; Christoph W TURCK ; Yuhui CHEN ; Longbao LV ; Yingzhou HU ; Hao LI ; Wenchao WANG ; Dongdong QIN ; Xiaoli FENG ; Xintian HU
Journal of Zhejiang University. Science. B 2024;25(11):972-995
Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals
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Autism Spectrum Disorder
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Macaca mulatta
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Disease Models, Animal
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Behavior, Animal
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Macaca fascicularis
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Male
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Humans
7.Role of tumor-associated macrophages in osteosarcoma and the implications for targeted therapy
Yue ZELIN ; Wang TIANHUA ; Qu XINTIAN ; Gong HAOQUAN ; Li NIANHU
Chinese Journal of Clinical Oncology 2024;51(24):1285-1290
Osteosarcoma(OS)is a common primary malignant bone tumor occurring predominantly in children and adolescents.The main treatments for OS are surgical resection and chemotherapy.Although overall survival rates have improved,progress has stalled in recent years,particularly in cases of recurrence and metastasis.The tumor microenvironment(TME)is closely related to tumor development,and macrophages are among the most abundant immune cells within the tumor environment.As a new target for tumor immunotherapy,mac-rophages have gained increasing attention due to their significant role in tumor progression.In this review,we explore the role of macro-phages in the OS microenvironment and discuss their clinical significance and involvement in the occurrence and development of OS.Fur-thermore,we summarize the therapeutic strategies targeting macrophages for OS treatment.
8.Atrial fibrillation detection using millimeter-wave radar
Hengji ZHOU ; Yihan YANG ; Yuanhui HU ; Yuguang CHU ; Xintian SHOU ; Yaping YOU ; Wenjing XUE ; Shaowei FAN ; Yong WANG ; Huiliang SHEN
Chinese Journal of Medical Physics 2024;41(1):81-87
A novel technology is proposed for non-contact and real-time detection of atrial fibrillation using millimeter-wave radar.A 60 GHz PCR millimeter wave radar is used to continuously detect the chest echo signal of the subject.After signal acquisition,I-Q signal is generated through I-Q demodulation,and the signal phase information is extracted using effective points phase trend evaluation for obtaining the signals from oscillations in the chest wall,from which the respiratory signals and cardiac signals are extracted through digital filtering for the analysis of cardiac movement.Whether the atrial fibrillation occurs or not is determined by the characteristics of atrial fibrillation wave in the time domain.The effective points phase trend evaluation for extracting more accurate signal phase information and the time-domain method for real-time atrial fibrillation detection are the innovations of the study.The experimental results show that the proposed method achieves a detection accuracy of 99.2%in clinic.
9.Research on Objective Characteristics of Tongue Manifestation in 315 Patients with Coronary Heart Disease
Mengyao DUAN ; Chuhao WANG ; Yuquan TAN ; Kun LIAN ; Xintian SHOU ; Yang JIANG ; Boyan MAO ; Zhixi HU
Journal of Traditional Chinese Medicine 2024;65(9):921-927
ObjectiveTo investigate the objective characteristics of tongue manifestations in patients with coronary heart disease (CHD). MethodsA total of 315 participants with CHD were recruited in the CHD group, and 211 healthy participants who underwent physical examination were recruited as the healthy control group. In addition, according to the common comorbidities (primary hypertension, carotid atherosclerosis, type 2 diabetes mellitus, fatty liver, hyperlipidaemia, heart failure, and cerebral infarction) in 315 participants with CHD, each comorbidity was classified into a group of comorbidities with that disease and a group of non-comorbidities. Tongue images were captured using a TFDA-1 tongue diagnostic instrument to characterise the tongue body (TB) and tongue coating (TC), comparing the RGB, HIS, and Lab colour spaces in the chromaticity index (R, red; G, green; B, blue; H, hue; I, intensity; S, saturation; L, lightness; a, red-green axis; b, yellow-blue axis), the tongue coating thickness index (per-All), contrast (CON), angular second moment (ASM), entropy (ENT), and mean (MEAN) in texture metrics. ResultsCompared with the healthy control group, the characteristic indexes of tongue body in CHD group showed lower TB-R, TB-G, TB-B, TB-I, TB-L and higher TB-H, TB-b; and the characteristic indexes of tongue coating in CHD group showed lower TC-R, TC-B and higher TC-CON, TC-MEAN, TC-H, TC-b (P<0.05 or P<0.01). Compared with non-combined primary hypertension group, CHD combined primary hypertension group showed higher per-All, TB-G, TB-L, and lower TB-a, TC-a (P<0.05); compared with the non-combined carotid atherosclerosis group, CHD combined carotid atherosclerosis group showed higher TB-CON, TB-ENT, TB-MEAN, and lower TB-ASM (P<0.05 or P<0.01); compared with the non-combined type 2 diabetes mellitus group, CHD combined type 2 diabetes mellitus group showed lower per-All and higher TB-H (P<0.05 or P<0.01); compared with the non-combined fatty liver group, CHD combined fatty liver group showed higher TB-CON, TB-MEAN, TB-ENT, and lower TB-ASM and TC-S (P<0.05 or P<0.01); compared with the non-combined hyperlipidaemia group, CHD combined hyperlipidaemia group showed lower TB-S and TB-a (P<0.05); compared with non-combined heart failure group, CHD combined heart failure group showed lower TB-R, TB-G, TB-I, TB-L, and higher TB-a (P<0.05 or P<0.01); compared with non-combined cerebral infarction group, CHD combined cerebral infarction group showed higher TC-CON, TC-ENT, TC-MEAN, and lower TC-ASM (P<0.05 or P<0.01). ConclusionCompared to healthy individuals, patients with CHD tend to have darker tongue colours and rougher TC textures. Compared with non-comorbidity participants, those with primary hypertension tended to be lighter tongue colour and thicker tongue coating, those with carotid atherosclerosis had paler tongue body, those with type 2 diabetes mellitus had thinner tongue coating, those with fatty liver disease had paler tongue body and whiter tongue colour, those with hyperlipidaemia and heart failure had paler tongue colour, and those with cerebral infarction had rougher tongue texture.
10.In vivo study of antibacterial carbon dot-modified polyether ether ketone to improve osseointegration of implants for treating MRSA infection environments
Hongxing HE ; Xintian ZHANG ; Menghan ZHANG ; Yao WANG ; Xiaoqin DENG ; Shaohuang WENG
Acta Laboratorium Animalis Scientia Sinica 2024;32(11):1408-1416
Objective This study aimed to evaluate the bone integration performance of antibacterial carbon dot(CD)-modified polyether ether ketone(PEEK)in infectious bone defect environments.Methods Guanidine-based CDs(G-CDs)prepared by the melting method combined with dialysis purification were used to modify PEEK implants using polyvinyl butyraldehyde(PVB)by the soaking-drying method(PEEK/PVB-G-CDs).SD rats were divided into the following groups:(1)PEEK-implanted uninfected(PEEK(-)),(2)PEEK/PVB-G-CDs-implanted uninfected(PEEK/PVB-G-CDs(-)),(3)PEEK-implanted infected(PEEK(+)),and(4)PEEK/PVB-G-CDs-implanted infected(PEEK/PVB-G-CDs(+)).A hole(diameter 2 mm,depth 5 mm)was drilled at the lateral condyle of the vertical femur in all rats to simulate a bone defect.Rats in the PEEK(-)and PEEK/PVB-G-CDs(-)groups without infection were injected with 30 μL physiological saline into the bone marrow cavity,and rats in the PEEK(+)and PEEK/PVB-G-CDs(+)groups with infection were injected with 30 μL MRSA bacterial suspension(1.5 × 104 colony-forming units/mL)into the bone marrow cavity.The implantation site was observed using animal-specific X-ray examination at 0,2,and 4 weeks after implantation,and the bone tissue characteristics of the implantation site were evaluated by micro computed tomography(CT)at 6 weeks after surgery.The bone implantation sites in each group of rats were examined by bacterial culture of bone marrow and hematoxylin and eosin staining,Toluidine blue,Goldner trichrome,and immunohistochemical staining.Results X-ray,Micro-CT,bacterial culture of bone marrow,and histopathological analysis confirmed no signs of infection in the PEEK(-)and PEEK/PVB-G-CDs(-)groups and the implants were integrated with the bone defects.Rats in the PEEK/PVB-G-CDs(+)group showed signs of antibacterial activity that effectively controlled the osteomyelitis caused by MRSA and achieved bone integration,while rats in the PEEK(+)group failed to achieve bone integration because of persistent infection.Immunohistochemical staining confirmed lower levels of anti-inflammatory factors such as IL-4 and IL-10 in the PEEK(+)group,and stronger expression of pro-inflammatory factors such as IL-6 and TNF-α compared with the other three groups,indicating that G-CD-modified PEEK inhibited MRSA infection,regulated inflammation levels in the local microenvironment,and promoted bone integration at the site of bone defects.Conclusions Antibacterial G-CDs modified PEEK exhibits excellent bone integration performance,providing a candidate strategy for future clinical treatment of infectious bone defects.

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