1.Research progress on cell mechanics and extracellular matrix mechanics in tumor therapy
ZHANG Hui ; GAO Hui ; XIE Youxiang ; YU Dongsheng
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(10):896-907
During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.
2.Two golden hamster models of hypervirulent Klebsiella pneumoniae respiratory infection:a comparative study
Zhijun ZHANG ; Lili ZHANG ; Meng LÜ ; Dongsheng ZHOU ; Wenhui YANG ; Bo GAO
Military Medical Sciences 2024;48(1):30-35
Objective To establish two golden hamster models infected with hypervirulent Klebsiella pneumoniae via aerosolized intratracheal(i.t.)and intranasal(i.n.)inoculation,and compare their properties.Methods Golden hamsters of 4 to 5 weeks old were exposed to K.pneumoniae NTUH-K2044 via i.t.route and i.n.route respectively.The survival of these golden hamsters was observed and recorded within 14 days of infection before the 50%lethal dose(LD50),survival rate,bacterial respiratory deposition rate,lung bacterial load and histopathology of the infected golden hamsters in the two groups were detected.Results The LD50 of the i.t.route(3×104 CFU)was lower than that of the i.n.route(7×105 CFU)in golden hamsters.After 4×106 CFU NTUH-K2044 infection,the golden hamsters in the i.t.group had 96.46%of the bacteria deposited and colonized in the lung,developed lobar pneumonia and died without exception within 4 days of infection,while those in the i.n.group had 95.62%of the bacteria deposited in the mouth and nose initially before the bacteria moved down to the trachea for colonization and were cleared out gradually.This group mainly acquired bronchopneumonia with relatively mild lung lesions,with a 14-day survival rate of 70%.Conclusion Inoculation routes can make a difference to the disease type of respiratory tract infections in animal models.The i.t.route mainly causes lobar pneumonia with severe lung lesions,while the i.n.route leads to bronchopneumonia with mild lung lesions.The two animal models established above may be utilized for pathogenesis investigation and treatment efficacy evaluation of Klebsiella pneumoniae.
3.Construction of the pore-forming toxin gene exlA knock-out mutant of Pseudomonas aeruginosa and its basic characteristics
Zaiqing ZHANG ; Yuanyuan ZHOU ; Lingfei HU ; Xiuyu JIN ; Dongsheng ZHOU ; Bo GAO ; Huiying YANG
Military Medical Sciences 2024;48(2):108-114
Objective To construct a non-trace deletion mutant of exlA in Pseudomonas aeruginosa strain NY8755(NY8755ΔexlA)and investigate the basic characteristics of pore-forming toxin ExlA.Methods The NY8755ΔexlA was constructed using the secondary homologous recombination method.C57BL/6J female mice ages 6 to 8 weeks were infected with NY8755 and NY8755 ΔexlA via aerosolized intratraheal inoculation respectively.Within 7 days of infection,the survival and weight changes of the mice were observed and recorded before the proinflammatory cytokines in the bronchoal-veolar lavage fluid(BALF)of the infected mice in the two groups were detected.Results The sequencing results showed that NY8755 ΔexlA was constructed.After 1×107 CFU NY8755 and NY8755 ΔexlA were infected,all the mice in the wild-type strain group died within 48 hours,while those in the mutant strain group began to die after 48 hours,and 40%of them remained alive 7 days later.The weight of surviving mice in the mutant strain group decreased but recovered gradually.After 12 hours of infection,there were more bloody exudates(redder in color)in the BALF of the wild-type strain group than in the mutant strain group,and the contents of proinflammatory cytokines interleukin-1β(IL-1β)and interleukin-17A (IL-17A)were significantly different. Conclusion Pseudomonas aeruginosa pore-forming toxin ExlA is the key pathogenic virulence factor of the exlA-positive Pseudomonas aeruginosa,which can significantly affect the survival status of mice and cause obvious inflammation in mice. Very little information is available on the action mechanisms of ExlA. In this study, The NY8755ΔexlA and the C57BL/6J mouse models infected with NY8755 and NY8755ΔexlA have been constructed that may be used for the investigation of pathogenesis of exlA-positive Pseudomonas aeruginosa.
4.Uyghur Medicine Yangxin Dawayimixike Honey Paste (养心达瓦依米西克蜜膏) in Treatment of 279 Cases Stable Angina Pectoris Patients with Qi Stagnation and Blood Stasis Syndrome:A Multi-center,Double-blind,Positive-controlled Randomized Clinical Trial
Binghua JIANG ; Lihua FAN ; Xiaofeng WANG ; Yingmin SONG ; Yanlai ZHANG ; Songyan QIAO ; Jing DONG ; Lihua JIN ; Yanping DING ; MAINISHA·MAIMAITI ; Jixian ZHAO ; Dongsheng GAO ; Qiuping ZHAO ; Lingxia GUAN ; Hongbin SUN ; Meise LIN ; Hengliang WANG ; Jun LI
Journal of Traditional Chinese Medicine 2024;65(21):2225-2233
ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste (养心达瓦依米西克蜜膏, YDMHP) in the treatment of stable angina pectoris (SAP) of qi stagnation and blood stasis syndrome. MethodsA randomized , double-blind, positive-controlled,multi-center clinical trial was conducted, in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group(279 cases)and control group(91cases)at a ratio of 3∶1. The treatment group was orally administered with YDMHP, 3 g each time, and placebo of Xuefu Zhuyu Capsule (血府逐瘀胶囊), 2.4 g each time, while the control group was treated with Xuefu Zhuyu Capsule, 2.4 g each time, and placebo of YDMHP, 3 g each time, both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks, duration of attacks, pain intensity and usae of nitroglycerin scores, the total angina symptom score before and after the treatment, the usage of nitroglycerin, the exercise duration in treadmill exercise test (TET) and the Duck treadmill score among patients,the scores of Seattle Angina Questionnaire (SAQ) on five dimensions including physical limitations, anginal stability, anginal frequency, treatment satisfaction, and disease perception, and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine, urine routine, liver and kidney function, fasting blood sugar, electrocardiogram, adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% (200/279), significantly higher than 51.64% (47/91) in the control group (P<0.01). The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% (148/279), which was significantly higher than 25.27% (23/91) in the control group (P<0.01). After treatment, scores of the number as well as duration of angina attacks and pain severity, the total score of angina symptoms, and the usage of nitroglycerin significantly decreased in both groups, and more changes were seen in the treatment group than in the control group; the scores of physical limitations, anginal stability, anginal frequency, treatment satisfaction, and disease perception in both groups significantly increased, and more improvement were shown in the experimental group regarding the anginal stability, anginal frequency and treatment satisfaction (P<0.05 or P<0.01). The effects of chest pain, chest tightness, palpitation, shortness of breath and fatigue in experimental group were significantly higher than those in control group (P<0.05 or P<0.01). There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment (P>0.05). Adverse events occurred in 66 cases (23.66%) of the experimental group and 16 cases (17.58%) of the control group, with no statistical significance between the two groups (P>0.05). ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris, reduce the number, duration, and intensity of attacks, decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.
5.The relationship between enlarged perivascular spaces in the hippocampus and cognitive function in patients with type 2 diabetes mellitus
Peichun PAN ; Jie GAO ; Jing LI ; Jialu SUN ; Dongsheng ZHANG ; Min TANG ; Xiaoling ZHANG
Journal of Practical Radiology 2024;40(9):1399-1402
Objective To investigate the relationship between enlarged perivascular spaces in the hippocampus(H-EPVS)and cognitive function in patients with type 2 diabetes mellitus(T2DM),and to explore whether the H-EPVS can be used as an imaging marker of cognitive impairment in T2DM.Methods A total of 93 T2DM patients were selected(including 56 patients with cognitive impair-ment and 37 patients with normal cognition).All patients received head MRI scanning and neuropsychological tests.The differences of the H-EPVS counts and various parameters between the two groups were compared.Multiple linear regression was used to evalu-ate the association between H-EPVS and cognitive function.Results Compared with the T2DM patients with normal cognition,the cognitive impairment had significantly higher total H-EPVS counts(P=0.015),and worse performance of global cognitive function,processing speed,immediate memory and delayed recall(P<0.05).After adjusting for confounding factors by multiple linear regres-sion,total H-EPVS were associated with global cognitive function and immediate memory.Conclusion The H-EPVS are correlated with global cognitive function and memory function in patients with T2DM.The H-EPVS may be used as an imaging marker of cog-nitive impairment in T2DM patients.
6.Prospective multicenter cohort study on breast cancer screening using an automated breast ultrasound with remote reading
Xiaozhi DANG ; Yi GAO ; Xiang GU ; Yan JU ; Dongsheng YI ; Huan LIN ; Yi REN ; Xiaojie YUAN ; Hongping SONG
Chinese Journal of Oncology 2024;46(11):1067-1075
Objective:To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening.Methods:We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations.Results:In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or Ⅰ breast cancers.Conclusions:Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.
7.Prospective multicenter cohort study on breast cancer screening using an automated breast ultrasound with remote reading
Xiaozhi DANG ; Yi GAO ; Xiang GU ; Yan JU ; Dongsheng YI ; Huan LIN ; Yi REN ; Xiaojie YUAN ; Hongping SONG
Chinese Journal of Oncology 2024;46(11):1067-1075
Objective:To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening.Methods:We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations.Results:In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or Ⅰ breast cancers.Conclusions:Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.
8.Mental health service utilization of patients with five mental disorders in Inner Mongolia communities
Yinxia BAI ; Lu TONG ; Zhaorui LIU ; Jie YAN ; Ruiqi WANG ; Tingting ZHANG ; Hua DING ; Lixia CHEN ; Jiahui YAO ; Xiaojuan GAO ; Dongsheng LYU ; Zhijian BAI ; Ziyu LI ; Xiaojie SUI ; Yueqin HUANG
Chinese Mental Health Journal 2024;38(5):419-425
Objective:To describe the current situation of mental health service utilization of community pa-tients with five mental disorders in Inner Mongolia Autonomous Region and provide reference for health education and formulating relevant policies.Methods:The multistage stratified sampling method with unequal probability was used to select a total of 12 315 community residents aged 18 and over in Inner Mongolia Autonomous Region.Using Composite International Diagnostic Interview,mood disorders,anxiety disorders,substance use disorders,intermit-tent explosive disorders,and eating disorders,and health service utilization were investigated.Descriptive statistics was completed by single factor analysis method.Results:The lifetime rates of consultation and treatment of any mental disorder were 18.7%and 10.2%,respectively.The highest proportion of patients received treatment by non-medical professionals was 31.4%,followed by psychiatrists in psychiatric hospital or psychologists in general hospitals.Among the patients,1.1%of them received medication,and 2.5%received psychotherapy.Conclusion:The utilization rate of mental health services in community patients with five mental disorders is relatively low.It is necessary to conduct health education for medical help seeking properly.
9.Shaoyaotang and Its Modified Formulas in Treatment of Ulcerative Colitis: A Review
Yanhong LI ; Dongsheng WU ; Yi LU ; Xingci LIU ; Yuting YANG ; Nianjia XIE ; Ya GAO ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):37-45
Shaoyaotang is composed of Cptidis Rhizoma, Scutellariae Radix, Rhei Radix et Rhizoma, Paeoniae Radix Alba, Angelicae Sinensis Radix, Aucklandiae Radix, Arecae Semen, Cinnamomi Cortex and Glycyrrhizae Radix et Rhizoma, with the functions of clearing away heat, eliminating dampness, regulating Qi and activating blood. Thus, it is proposed as the main formula for the treatment of dampness-heat dysentery by later generations of doctors. In modern clinical application, in addition to original Shaoyaotang, its modified formulas are also used for the treatment of ulcerative colitis, and can be used in combination with other prescriptions (such as Tongxie Yaofang, Pulsatilla Soup, Shenling Baizhu San), western medicine (such as mesalazine, sulfasalazine, Infliximab), traditional Chinese medicine (TCM) acupuncture or moxibustion and other characteristic therapies. Clinical efficacy results indicate that Shaoyaotang and its modified formulas can significantly lower Mayo Endoscopic Score (MES), Baron score, TCM syndrome score and other disease scores, and improve patients’ intestinal symptoms, with few side effects. Experimental pharmacological studies reveal that Shaoyaotang can inhibit tumor necrosis factor-α (TNF-α), nuclear transcription factor-κB (NF-κB), interleukin-1β (IL-1β) and other pro-inflammatory factors to up regulate the expression of anti-inflammatory factors such as interleukin-10 (IL-10), thereby reducing the inflammatory response. The formula could also reduce apoptosis by regulating inflammatory signaling pathway and blocking the chain reaction, and repair abnormal immune barrier by balancing immune axis and regulating immune proteins. Additionally, it could adjust the balance of intestinal flora, promote intestinal epithelial cell regeneration and improve mucosal permeability, so as to restore the balance of intestinal environment and thus treat ulcerative colitis. Its monomers baicalin, paeoniflorin, and berberine have anti-inflammatory, antibacterial, metabolism-regulating and other effects. This paper systematically reviewed the clinical and basic research progress of Shaoyaotang in the treatment of ulcerative colitis.
10.Establishment of a patient-derived xenograft humanized mouse model for hepatoblastoma in children
Huimin HU ; Weiling ZHANG ; Dongsheng HUANG ; Rui LI ; Huali GU ; Jing LI ; Yanan GAO
Chinese Journal of Hepatology 2023;31(10):1075-1080
Objective:To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor.Methods:A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children’s data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ2 test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results:After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma’s PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, β-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion:A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.


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