1.A novel exploration of COL11A1's role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment.
Wei NIU ; Xiaxia DU ; Yang SONG ; Lianyi GUO ; Baohai LIU ; Xin TONG
Journal of Pharmaceutical Analysis 2025;15(4):101181-101181
This study aimed to elucidate the role of collagen type XI alpha 1 (COL11A1)-positive cancer-associated fibroblasts (CAFs) in modifying the tumor microenvironment of colon cancer (CC) and facilitating immune evasion through interactions with myeloid-derived suppressor cells (MDSCs). Using single-cell transcriptomic sequencing, we analyzed the interplay between COL11A 1-positive CAFs and MDSCs in the CC microenvironment, focusing on how COL11A1 impacts MDSC differentiation and activation. The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase (MMP)3 and MMP13 expression, leading to paracrine induction of MDSC differentiation and activation, which promotes immune evasion and tumor growth. Additionally, we observed that COL11A1 knockout (COL11A1KO) suppresses tumor growth and hinders immune evasion. These findings underscore the essential role of COL11A 1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression. By elucidating the molecular pathway through which COL11A1 influences MDSC activity, this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC, particularly through modulating COL11A1 expression in CAFs.
2.A prospective randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer
Hao ZHANG ; Yiying ZHU ; Weiwei OUYANG ; Shengfa SU ; Zhu MA ; Qingsong LI ; Yichao GENG ; Wengang YANG ; Xiaxia CHEN ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(1):65-72
Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.
3.A prospective study on clinical monitoring of early cardiac myocardial dysfunction by conventional radiotherapy in N 2-N 3 non-small cell lung cancer with lymph node metastases
Yiying ZHU ; Hao ZHANG ; Weiwei OUYANG ; Shengfa SU ; Yinxiang HU ; Zhu MA ; Sha LI ; Qingsong LI ; Wengang YANG ; Xiaxia CHEN ; Haijie JIN ; Jie LIU ; Fuhuan LUO ; Zhourui LIU ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(7):664-670
Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.
4.A novel exploration of COL11A1's role in regulating myeloid-derived suppressor cell activation within the colon cancer microenvironment
Wei NIU ; Xiaxia DU ; Yang SONG ; Lianyi GUO ; Baohai LIU ; Xin TONG
Journal of Pharmaceutical Analysis 2025;15(4):835-852
This study aimed to elucidate the role of collagen type Ⅺ alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating im-mune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.
5.A prospective randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer
Hao ZHANG ; Yiying ZHU ; Weiwei OUYANG ; Shengfa SU ; Zhu MA ; Qingsong LI ; Yichao GENG ; Wengang YANG ; Xiaxia CHEN ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(1):65-72
Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.
6.A prospective study on clinical monitoring of early cardiac myocardial dysfunction by conventional radiotherapy in N 2-N 3 non-small cell lung cancer with lymph node metastases
Yiying ZHU ; Hao ZHANG ; Weiwei OUYANG ; Shengfa SU ; Yinxiang HU ; Zhu MA ; Sha LI ; Qingsong LI ; Wengang YANG ; Xiaxia CHEN ; Haijie JIN ; Jie LIU ; Fuhuan LUO ; Zhourui LIU ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(7):664-670
Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.
7.Timing of stage Ⅱ vitrectomy in patients with open ocular trauma
Chunxia* MA ; Xiaxia* YANG ; Chaowei TIAN ; Manhong LI ; Dan HU ; Yusheng WANG ; Zifeng ZHANG
International Eye Science 2024;24(4):630-633
AIM:To observe the clinical efficacy of vitrectomy at different times for open ocular trauma and explore the timing of stage Ⅱ vitrectomy.METHODS: Retrospective case series study. A total of 60 cases(60 eyes)with open ocular trauma who visited our ophthalmology department from June 2022 to February 2023 were included. They were divided into treatment group A(interval ≤14 d)and treatment group B(interval >14 d)based on the interval between the stage Ⅰ emergency treatment surgery and the stage Ⅱ vitreoretinal surgery. Among the 32 cases(32 eyes)in the treatment group A, 16 eyes(50%)had eyeball rupture, 13 eyes(41%)had penetrating injury, and 3 eyes(9%)had perforating injury. Among the 28 cases(28 eyes)in the treatment group B, 15 eyes(54%)had eyeball rupture, 12 eyes(43%)had penetrating injury, and one eye(4%)had perforating injury. The two groups of patients were followed-up for 6 mo after surgery, and the treatment effects were compared.RESULTS:There was no statistically significant difference in visual acuity between the two groups of patients before vitrectomy(P>0.05). In the treatment group A, 10 eyes(31%)had significantly improved visual acuity, 21 eyes(66%)had effectively enhanced visual acuity, and 1 eye(3%)had no improvement in visual acuity at 6 mo after surgery. Among the 28 eyes in the treatment group B, 5 eyes(18%)had significantly improved vision, 16 eyes(57%)had effectively enhanced vision, and 7 eyes(25%)had no change in vision, with statistically significant difference between the two groups(U=322.5, P=0.032). There was no significant difference between the treatment group A and the treatment group B in complications such as secondary glaucoma, silicone oil dependence, vitreous hemorrhage, and eyeball atrophy(P>0.05). There was no evidence of traumatic proliferative vitreoretinopathy(TPVR)in the treatment group A during postoperative follow-up, which was significantly lower than that of the treatment group B(P<0.05).CONCLUSION:The prognosis of the stage Ⅱ vitrectomy for open ocular injury is relatively good after completing the stage Ⅰ surgery within 2 wk.
8.Clinical features and impact factors in patients with open ocular trauma
Xiaxia* YANG ; Chunxia* MA ; Pengfei LIU ; Chaowei TIAN ; Manhong LI ; Dan HU ; Yusheng WANG ; Zifeng ZHANG
International Eye Science 2024;24(11):1846-1850
AIM:To summarize the clinical features and prognostic factors of patients with open ocular trauma in northwest China, and to explore the application of ocular trauma score(OTS)in open ocular trauma.METHODS:The clinical data of 91 patients(91 eyes)with open ocular trauma admitted to Xijing Hospital from June 2021 to June 2023 were retrospectively analyzed. The correlation analysis of visual acuity prognosis was carried out by age, treatment time, initial visual acuity, trauma zone and other factors, and the relationship between different OTS and prognostic visual acuity was discussed.RESULTS:Univariate analysis showed that age(0-20 years), treatment time(<24 h), initial visual acuity, trauma zone, trauma type(penetrating injury), anterior chamber hematoma, vitreous hematoma were correlated with prognostic visual acuity(all P<0.1); multivariate Logistic regression analysis showed that initial visual acuity and treatment time(<24 h)were risk factors(both P<0.05). There was a significant correlation between different OTS and prognostic visual acuity(rs=0.639,P<0.001).CONCLUSION:Patients with open ocular trauma should be diagnosed and treated as early as possible. The main factors influencing the visual prognosis are age, treatment time, initial visual acuity, trauma zone, trauma type, anterior chamber hematoma and vitreous hematoma. OTS has good application value in visual acuity evaluation of open ocular trauma prognosis.
9.Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention
Zhao BINBIN ; Wei DONGFENG ; Long QINGHUA ; Chen QINGJIE ; Wang FUSHUN ; Chen LINLIN ; Li ZEFEI ; Li TONG ; Ma TAO ; Liu WEI ; Wang LINSHUANG ; Yang CAISHUI ; Zhang XIAXIA ; Wang PING ; Zhang ZHANJUN
Journal of Pharmaceutical Analysis 2024;14(3):348-370
Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.
10.Value of multiparametric MRI texture analysis in predicting axillary lymph node metastasis of small-sized breast cancer
Xiaxia HE ; Chao CHEN ; Xiaoping YANG ; Guoyu WANG
China Modern Doctor 2024;62(23):21-25
Objective To investigate the value of multiparametric magnetic resonance imaging(MRI)texture analysis based on T2 weighted image(T2WI),diffusion weighted imaging(DWI),and dynamic contrast enhanced-MRI(DCE-MRI)in predicting the axillary lymph node status of small-sized invasive ductal carcinoma(IDC)of the breast.Methods A retrospective analysis was conducted on the medical records of 139 patients with newly diagnosed IDC,who were treated at Taizhou Central Hospital from January 2018 to June 2023.Based on the postoperative pathological results,the patients were divided into two groups:85 cases without axillary lymph node metastasis and 54 cases with axillary lymph node metastasis.All patients underwent preoperative MRI examination,including sequences such as T2WI,DWI,and DCE-MRI.After delineating the region of interest(ROI)on the slice with the largest tumor diameter in each sequence,texture analysis was performed using Firevoxel software,which yielded five major parameters,including mean,standard deviation,skewness,kurtosis,and entropy.Univariate analysis was employed to evaluate the effectiveness of each parameter in distinguishing the axillary lymph node status.Variables that showed significant results in the univariate analysis were then included in binary Logistic regression analysis to explore the relationship between these parameters and lymph node metastasis status.Receiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was calculated.Results Significant differences were observed between the two groups in the entropy and mean values of the ROI delineated on the DCE-MRI sequence,as well as the skewness of the T2WI(P<0.001).Among these texture parameters,the entropy of the DCE-MRI sequence showed the highest AUC value of 0.719 in the univariate analysis.Multivariate analysis of the selected parameters yielded an optimal diagnostic model,with an AUC of 0.769 in differentiating lymph node metastasis from non-metastasis.Conclusion Texture analysis of small-sized breast cancer based on multiparametric MRI can effectively predict the preoperative axillary lymph node status of breast cancer.

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