1.Construction of an Evaluation System for Traditional Chinese Medicine Appropriate Technologies Based on Evidence-Based Medicine
Jixing WANG ; Zhiyi ZHOU ; Sisi LIN ; Dieyu MA ; Zhizhen ZHOU ; Conghua JI
Journal of Traditional Chinese Medicine 2026;67(4):355-359
Based on the theory of evidence-based medicine (EBM), this paper systematically constructed a multi-dimensional evaluation framework for traditional Chinese medicine (TCM) appropriate technologies, encompassing three core dimensions including evidence, practitioner, and patient. For the current practical challenges in the promotion of TCM technologies such as lack of high-quality evidence, inconsistent operational standards, and varying patient acceptance, the paper proposed the integration of published literature evidence and real-world research data to construct a scientific and applicable evaluation pathway. Regarding the evidence dimension, it emphasizes syste-matic assessment of effectiveness, safety, and economic efficiency, introducing methods like the target trial emulation framework to enhance evidence quality; for the practitioner dimension, it suggests developing multi-aspects competency evaluation tools based on educational background, training assessment, and clinical outcomes; for the patient dimension, it recommends designing patient acceptance assessment tools by considering factors such as technical characte-ristics, expected efficacy, patient-practitioner interaction, and the availability of alternative treatments. The purpose of the above measures is to provide methodological support for the standardized popularization and precision application of TCM appropriate technologies.
2.Influencing factors for calcium salt deposition in patients with alveolar echinococcosis
Zitong XIONG ; Zhiyi LIN ; Yanxin HUANG ; Fuzhong FANG ; Zhengzhan WU ; Zirui XIN ; Chunxia HU ; Jiayu ZHOU ; Yuan YAO ; Hongwei ZHANG
Journal of Clinical Hepatology 2026;42(2):372-379
ObjectiveTo investigate the imaging features of calcium salt deposition and serological markers in patients with alveolar echinococcosis through a retrospective analysis, as well as independent risk factors for the degree of calcium salt deposition in lesions, and to provide a basis for assessing disease process. MethodsA retrospective analysis was performed for the imaging and clinical data of 107 patients with alveolar echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from December 2023 to June 2025, and according to the volume of calcium salt deposition, they were divided into non-deposition group with 16 patients, mild deposition group with 52 patients, moderate deposition group with 16 patients, and severe deposition group with 23 patients. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups, and the χ2 test or Fisher’s exact test was used for comparison of categorical data between groups. The four groups were further combined into the low deposition group (no/mild deposition) and the high deposition group (moderate/severe deposition). A binary logistic regression analysis was used to investigate the independent influencing factors for calcium salt deposition, and a predictive model was established. The receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model, and the Bootstrap method was used for internal validation. ResultsThere were significant differences between the four groups in sex distribution, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.05). The univariate analysis showed that there were significant differences between the four groups in sex, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, alanine aminotransferase, albumin, creatinine, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.1). The multi-collinearity diagnosis showed that the VIF values for all continuous variables ranged from 1.104 to 1.760, suggesting that collinearity did not affect modeling. An ordinal logistic regression model was established based on sex, involvement of other sites, calcium ion, lymphocyte percentage, and uric acid. The multivariate analysis showed that lymphocyte percentage (odds ratio [OR]=1.106, 95% confidence interval [CI]: 1.041 — 1.174, P=0.001) and blood calcium level (OR=0.005, 95%CI: 0.000 —0.230, P=0.007) were independent influencing factors for the degree of calcium salt deposition. The regression equation was established as Logit(P)=8.231 + 0.100 × lymphocyte percentage -5.344 × calcium ion. The ROC curve analysis showed that the model had an area under the ROC curve of 0.716, with a Youden index of 0.353, a sensitivity of 1.000, and a specificity of 0.353. The Hosmer-Lemeshow test showed that the model had poor calibration (χ2=20.688, P=0.008). The Bootstrap method with 1000 repeated samples showed that the estimated values of lymphocyte percentage (OR=1.106, 95%CI: 1.049 — 1.186, P=0.002) and calcium ion (OR=0.005, 95%CI: 0.000 — 0.214, P=0.010) were consistent with the original model, and the confidence intervals did not include 1, which further supported the reliability of the model. ConclusionBoth lymphocyte percentage and blood calcium level are independent influencing factors for calcium salt deposition in alveolar echinococcosis, and the degree of calcium salt deposition in alveolar echinococcosis lesions increases with the reduction in blood calcium level and the increase in lymphocyte percentage.
3.Impact of 99Tcm-FAPI SPECT/CT on Diagnostic Efficacy and Immunotherapy Decision-Making in Advanced Colorectal Cancer
Yu ZHANG ; Zhiyi LIN ; Hong CHEN ; Mingdian YU ; Chenshen HUANG ; Wenxin CHEN
Chinese Journal of Medical Imaging 2025;33(7):768-774
Purpose To explore the diagnostic efficacy of 99Tcm labeled fibroblast activation protein inhibitor(FAPI)SPECT/CT for metastatic lesions in advanced colorectal cancer and its impact on decisions regarding immunotherapy,and to compare it with 18F-FDG PET/CT.Materials and Methods A total of 34 patients with advanced colorectal cancer who underwent both 99Tcm-FAPI SPECT/CT and 18F-FDG PET/CT imaging from August 2022 to November 2023 in Fuzhou University Affiliated Provincial Hospital were prospectively included.The gold standard was based on biopsy or clinical and imaging follow-up results.Chi-square tests and rank sum tests were used to compare differences between the groups.Results Among the 34 patients,17 patients subsequently received immunotherapy.The uptake of 99Tcm-FAPI was significantly higher than that of 18F-FDG for the primary tumor site(Z=-2.389,P=0.017),peritoneal metastasis(Z=-2.497,P=0.013)and liver metastasis(Z=-0.106,P=0.015).The diagnostic efficacy of 99Tcm-FAPI SPECT/CT for patients with peritoneal metastasis was superior to that of 18F-FDG PET/CT(χ2=4.65,P=0.033).Metastatic lesions that did not uptake 99Tcm-FAPI had a better clinical prognosis after immunotherapy(χ2=11.839,P=0.006),and maximum standardized uptake value(SUVmax)-FDG/SUVmax-FAPI ratio was a promising predictive factor for a better prognosis after immunotherapy,with an optimal cut-off value of 5.04.Conclusion 99Tcm-FAPI SPECT/CT has superior diagnostic efficacy for peritoneal metastasis in advanced colorectal cancer compared with 18F-FDG PET/CT.SUVmax-FDG/SUVmax-FAPI ratio is a promising radiomic parameter for predicting patient prognosis after immunotherapy,which can help guide clinical decision-making further.
4.Association between exposure to non-optimal temperature during pregnancy and preterm birth
Zhiyi GAO ; Liuyan ZHENG ; Shuting CAI ; Shiying WENG ; Libiao WU ; Jiaxin XU ; Shaowei LIN ; Huangyuan LI ; Jinying LUO ; Siying WU
Chinese Journal of Epidemiology 2025;46(5):874-879
Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.
5.Association between exposure to non-optimal temperature during pregnancy and preterm birth
Zhiyi GAO ; Liuyan ZHENG ; Shuting CAI ; Shiying WENG ; Libiao WU ; Jiaxin XU ; Shaowei LIN ; Huangyuan LI ; Jinying LUO ; Siying WU
Chinese Journal of Epidemiology 2025;46(5):874-879
Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.
6.Effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats
Sunlin GUO ; Enda HONG ; Xinhua DAI ; Xi LIN ; Zhiyi PENG ; Yingxiong CHENG ; Linyan FAN
Chinese Journal of Tissue Engineering Research 2025;29(26):5588-5594
BACKGROUND:Previous studies have found that for postmenopausal osteoporosis patients,the Bushen Jianpi Formula can help regulate serum osteoclast-and osteoblast-related factors and intestinal flora levels,improve clinical symptoms of patients and further improve efficacy.OBJECTIVE:To investigate the effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats.METHODS:Twenty-four female SD rats were randomly divided into four groups by random number table method:sham operation group(n=6)was subjected to periovarian fat removal,and bilateral ovariectomy was performed in model group(n=6),alendronate group(n=6),and Bushen Jianpi Formula group(n=6).Five days after modeling,the Bushen Jianpi Formula group was given Bushen Jianpi Formula by intragastric administration(once a day).The alendronate sodium group was given alendronate by intragastric administration(once a week).The sham operation group and model group were given an equal volume of normal saline by intragastric administration(once a day)for 12 consecutive weeks.After intragastric administration,serum levels of procollagen Ⅰ N-terminal peptide,β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation product,and tumor necrosis factor α were detected.The distal femur microstructure was detected by Micro-CT.The femoral tissue morphology was observed by hematoxylin-eosin staining.The expression of type Ⅰ collagen and tumor necrosis factorα in the femur was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The serum ELISA test showed that compared with the sham operation group,the level of procollagen Ⅰ N-terminal peptide in the model group decreased(P<0.05),and the levels of degradation products of β-isomerized C-terminal telopeptide of type Ⅰ collagen and tumor necrosis factor α increased(P<0.05).Compared with the model group,the levels of the procollagen Ⅰ N-terminal peptide in the Bushen Jianpi Formula group and the alendronate sodium group increased(P<0.05),and the levels of β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation products and tumor necrosis factor α decreased(P<0.05).(2)Micro-CT three-dimensional reconstruction showed that compared with the sham operation group,the number of bone trabeculae in the model group was significantly reduced,the continuity was worsened,and the gaps were increased.Both alendronate sodium and Bushen Jianpi Formula had a positive improvement effect on this phenomenon.(3)Hematoxylin-eosin staining showed that compared with the sham operation group,the number of bone trabeculae in the model group was reduced and the shape became thinner,and the network structure was destroyed.Compared with the model group,the number of bone trabeculae in the Bushen Jianpi Formula group and the alendronate sodium group increased,the shape became thicker,and the reticular structure was restored.(4)Immunohistochemical staining showed that compared with the sham operation group,the expression of type Ⅰ collagen was reduced and tumor necrosis factor α expression was increased in the model group.Compared with the model group,the expression of type Ⅰ collagen increased and the expression of tumor necrosis factor α decreased in the Bushen Jianpi Formula group and the alendronate sodium group.The results show that the Bushen Jianpi Formula can effectively improve bone metabolism and bone microstructure in ovariectomized rats.
7.Effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats
Sunlin GUO ; Enda HONG ; Xinhua DAI ; Xi LIN ; Zhiyi PENG ; Yingxiong CHENG ; Linyan FAN
Chinese Journal of Tissue Engineering Research 2025;29(26):5588-5594
BACKGROUND:Previous studies have found that for postmenopausal osteoporosis patients,the Bushen Jianpi Formula can help regulate serum osteoclast-and osteoblast-related factors and intestinal flora levels,improve clinical symptoms of patients and further improve efficacy.OBJECTIVE:To investigate the effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats.METHODS:Twenty-four female SD rats were randomly divided into four groups by random number table method:sham operation group(n=6)was subjected to periovarian fat removal,and bilateral ovariectomy was performed in model group(n=6),alendronate group(n=6),and Bushen Jianpi Formula group(n=6).Five days after modeling,the Bushen Jianpi Formula group was given Bushen Jianpi Formula by intragastric administration(once a day).The alendronate sodium group was given alendronate by intragastric administration(once a week).The sham operation group and model group were given an equal volume of normal saline by intragastric administration(once a day)for 12 consecutive weeks.After intragastric administration,serum levels of procollagen Ⅰ N-terminal peptide,β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation product,and tumor necrosis factor α were detected.The distal femur microstructure was detected by Micro-CT.The femoral tissue morphology was observed by hematoxylin-eosin staining.The expression of type Ⅰ collagen and tumor necrosis factorα in the femur was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The serum ELISA test showed that compared with the sham operation group,the level of procollagen Ⅰ N-terminal peptide in the model group decreased(P<0.05),and the levels of degradation products of β-isomerized C-terminal telopeptide of type Ⅰ collagen and tumor necrosis factor α increased(P<0.05).Compared with the model group,the levels of the procollagen Ⅰ N-terminal peptide in the Bushen Jianpi Formula group and the alendronate sodium group increased(P<0.05),and the levels of β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation products and tumor necrosis factor α decreased(P<0.05).(2)Micro-CT three-dimensional reconstruction showed that compared with the sham operation group,the number of bone trabeculae in the model group was significantly reduced,the continuity was worsened,and the gaps were increased.Both alendronate sodium and Bushen Jianpi Formula had a positive improvement effect on this phenomenon.(3)Hematoxylin-eosin staining showed that compared with the sham operation group,the number of bone trabeculae in the model group was reduced and the shape became thinner,and the network structure was destroyed.Compared with the model group,the number of bone trabeculae in the Bushen Jianpi Formula group and the alendronate sodium group increased,the shape became thicker,and the reticular structure was restored.(4)Immunohistochemical staining showed that compared with the sham operation group,the expression of type Ⅰ collagen was reduced and tumor necrosis factor α expression was increased in the model group.Compared with the model group,the expression of type Ⅰ collagen increased and the expression of tumor necrosis factor α decreased in the Bushen Jianpi Formula group and the alendronate sodium group.The results show that the Bushen Jianpi Formula can effectively improve bone metabolism and bone microstructure in ovariectomized rats.
8.Impact of 99Tcm-FAPI SPECT/CT on Diagnostic Efficacy and Immunotherapy Decision-Making in Advanced Colorectal Cancer
Yu ZHANG ; Zhiyi LIN ; Hong CHEN ; Mingdian YU ; Chenshen HUANG ; Wenxin CHEN
Chinese Journal of Medical Imaging 2025;33(7):768-774
Purpose To explore the diagnostic efficacy of 99Tcm labeled fibroblast activation protein inhibitor(FAPI)SPECT/CT for metastatic lesions in advanced colorectal cancer and its impact on decisions regarding immunotherapy,and to compare it with 18F-FDG PET/CT.Materials and Methods A total of 34 patients with advanced colorectal cancer who underwent both 99Tcm-FAPI SPECT/CT and 18F-FDG PET/CT imaging from August 2022 to November 2023 in Fuzhou University Affiliated Provincial Hospital were prospectively included.The gold standard was based on biopsy or clinical and imaging follow-up results.Chi-square tests and rank sum tests were used to compare differences between the groups.Results Among the 34 patients,17 patients subsequently received immunotherapy.The uptake of 99Tcm-FAPI was significantly higher than that of 18F-FDG for the primary tumor site(Z=-2.389,P=0.017),peritoneal metastasis(Z=-2.497,P=0.013)and liver metastasis(Z=-0.106,P=0.015).The diagnostic efficacy of 99Tcm-FAPI SPECT/CT for patients with peritoneal metastasis was superior to that of 18F-FDG PET/CT(χ2=4.65,P=0.033).Metastatic lesions that did not uptake 99Tcm-FAPI had a better clinical prognosis after immunotherapy(χ2=11.839,P=0.006),and maximum standardized uptake value(SUVmax)-FDG/SUVmax-FAPI ratio was a promising predictive factor for a better prognosis after immunotherapy,with an optimal cut-off value of 5.04.Conclusion 99Tcm-FAPI SPECT/CT has superior diagnostic efficacy for peritoneal metastasis in advanced colorectal cancer compared with 18F-FDG PET/CT.SUVmax-FDG/SUVmax-FAPI ratio is a promising radiomic parameter for predicting patient prognosis after immunotherapy,which can help guide clinical decision-making further.
9.Prevalence of frailty and related factors in middle-aged and elderly people in island and mountainous areas of Taizhou, Zhejiang Province
Xinyue LIANG ; Qionggui ZHOU ; Liangyou WANG ; Shaling WANG ; Yali XIE ; Xuan YANG ; Jiayu HE ; Zhiyi ZHANG ; Miaochen WANG ; Shuxian HE ; Yunqiu ZHANG ; Tailin CHEN ; Xuanhe WU ; Tingting WANG ; Haijiang LIN ; Xiaoxiao CHEN ; Na HE
Chinese Journal of Epidemiology 2024;45(1):139-147
Objective:To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province.Methods:Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty.Results:A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (a OR=1.55,95% CI: 1.07-2.25, P=0.019). In island area, older age (60-74 years:a OR=2.52,95% CI: 1.56-4.13; ≥75 years:a OR=11.65,95% CI:5.38-26.70), being women (a OR=1.94,95% CI: 1.20-3.17), suffering from depression (a OR=1.09,95% CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: a OR=1.74,95% CI:1.04-2.94;≥75 years: a OR=4.78,95% CI:2.45-9.50). Polydrug use (a OR=2.08,95% CI: 1.14-3.80) and suffering from depression (a OR=1.10,95% CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: a OR=0.40,95% CI: 0.21-0.75; senior high school and technical secondary school: a OR=0.29,95% CI: 0.15-0.53; college or above:a OR=0.22,95% CI: 0.11-0.42). Conclusions:The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.
10.SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice.
Lingling GAO ; Zhi XIE ; Shouheng LIN ; Zhiyi LV ; Wenbin ZHOU ; Ji CHEN ; Linlin ZHU ; Li ZHANG ; Penghui ZENG ; Xiaodan HUANG ; Wenqing YAN ; Yu CHEN ; Danxia LU ; Shuilian ZHANG ; Weibang GUO ; Peng LI ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2023;26(10):753-764
BACKGROUND:
The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex.
METHODS:
The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases.
RESULTS:
WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group.
CONCLUSIONS
This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals
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Mice
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Carcinoma, Non-Small-Cell Lung/genetics*
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Lung Neoplasms/genetics*
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Mutation
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Liver Neoplasms/genetics*

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