1.Effect of Go-Ichi-Ni-San complex subunit 1 on disease progression and chemotherapy resistance in hepatocellular carcinoma
Yishan HUO ; Dawei LI ; Xiangbing DUAN ; Yuyu MA ; Guojun ZHANG ; Kainan ZHANG ; Xiumin MA
Journal of Clinical Hepatology 2025;41(3):485-492
ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 (GINS1) in the progression of hepatocellular carcinoma (HCC) and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals, and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue, and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity; scratch assay was used to measure cell migration ability; Transwell assay was used to measure cell invasion ability; cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients, HCC tissue, and HCC cell lines (all P<0.05), and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC (r=0.822, P=0.011). Compared with the negative control cells, the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation, migration, and invasion activities (all P<0.01) and a significantly enhanced sensitivity to oxaliplatin (P<0.01). Compared with the nude mice in the control group, GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice (all P<0.001). Compared with the negative control cells, the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1, Notch3, p-JAK2, and p-STAT3 (all P<0.05), while there were no significant differences in the overall expression levels of JAK2 and STAT3 (P>0.05). After Jagged-1 treatment, the GINS1-knockdown MHCC97H cells showed significant increases in proliferation, migration, and invasion activities and a significant reduction in sensitivity to oxaliplatin, as well as significant increases in the levels of p-JAK2 and p-STAT3 (all P<0.05). ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.
2.Proximal pericolic lymph node metastasis beyond 10 cm in rectal cancer: patterns of prognostic impact of extended resection in a prospective cohort study
Xuyang YANG ; Yang ZHANG ; Lina YE ; Qingbin WU ; Tinghan YANG ; Mingtian WEI ; Xiangbing DENG ; Haining CHEN ; Wenjian MENG ; Ziqiang WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1015-1025
Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.
3.Proximal pericolic lymph node metastasis beyond 10 cm in rectal cancer: patterns of prognostic impact of extended resection in a prospective cohort study
Xuyang YANG ; Yang ZHANG ; Lina YE ; Qingbin WU ; Tinghan YANG ; Mingtian WEI ; Xiangbing DENG ; Haining CHEN ; Wenjian MENG ; Ziqiang WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1015-1025
Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.
4.MRI study of the relationship between the cerebral small vessel disease total burden and imaging markers and degree of middle cerebral artery stenosis
Xinbo XING ; Xueyang WANG ; Jinhao LYU ; Qi DUAN ; Caohui DUAN ; Xiangbing BIAN ; Kun CHENG ; Mingliang YANG ; Tingyang ZHANG ; Chenglin TIAN ; Xin LOU
Chinese Journal of Radiology 2024;58(1):34-40
Objective:To investigate the relationship between the cerebral small vascular disease (CSVD) total burden and the imaging markers and the degree of unilateral middle cerebral artery (MCA) stenosis.Methods:The study was a cross-sectional study. Clinical and imaging data of patients with chronic unilateral MCA stenosis who underwent multimodal MRI from October 2015 to January 2019 in the First Medical Center of PLA General Hospital were retrospectively analyzed. A total of 261 patients were included, 187 males and 74 females. According to the degree of MCA stenosis, the patients were divided into 102 cases in severe stenosis-occlusion group (stenosis degree ≥70%) and 159 cases in mild-moderate stenosis group (stenosis degree <70%). CSVD imaging marker scores (including white matter hyperintensity, perivascular space, cerebral microbleed, and lacune of presumed vascular origin) were assessed according to the ?standards for reporting vascular changes on neuroimaging 1 in the 2 groups, and the CSVD total burden score was calculated. Mann-Whitney U test was used to compare the indicators between the two groups, and the CSVD total burden score and imaging marker scores were ultimately included in a multifactorial binary logistic regression to assess the association of CSVD imaging markers with severe stenosis-occlusion of the MCA after adjusting for vascular risk factors (age, gender, drinking, smoking, hypertension, hyperlipidemia, atrial fibrillation and coronary heart disease). Results:There were significant differences in the CSVD total burden, centrum semiovale perivascular space and lacune of presumed vascular origin score between the mild-to-moderate stenosis group and the severe stenosis-occlusion group (all P<0.05), and none of the differences in the remaining imaging marker scores were statistically significant (all P>0.05). Multivariate binary logistics regression analysis showed CSVD total burden score ( OR=1.300, 95% CI 1.047-1.613, P=0.017), centrum semiovale perivascular space score ( OR=2.099, 95% CI 1.540-2.860, P<0.001) and lacune of presumed vascular origin score ( OR=2.609, 95% CI 1.294-5.261, P=0.007) were independent associated with severe stenosis-occlusion of MCA. Conclusion:The higher CSVD total burden score, centrum semiovale perivascular space score and lacune of presumed vascular origin score are associated with severe stenosis-occlusion of MCA.
5.Application of fast susceptibility weighted imaging based on deep learning in assessment of acute ischemic stroke
Qi DUAN ; Caohui DUAN ; Shiqing ZHOU ; Jinhao LYU ; Xiangbing BIAN ; Dekang ZHANG ; Kun CHENG ; Mingliang YANG ; Xueyang WANG ; Tingyang ZHANG ; Xinbo XING ; Chenglin TIAN ; Xin LOU
Chinese Journal of Radiology 2023;57(1):34-40
Objective:To explore the value of fast susceptibility weighted imaging (SWI) generated by a deep learning model in assessment of acute ischemic stroke (AIS).Methods:From January 2019 to January 2021, 118 AIS patients [75 males and 43 females, aged 23-100 (66±14) years] who underwent MR examination and SWI sequence scanning within 24 h of symptom onset in the First Medical Center of PLA General Hospital were retrospectively analyzed. MATLAB ′s randperm function was used to divide 118 patients into a training set of 96 cases and a test set of 22 cases at a ratio of 8∶2. Fourty-seven AIS patients [38 males and 9 females, aged 16-75 (58±12) years] from one center of a multicenter study were selected to build the external validation set. SWI image and filtered phase image were combined into complex value image as full sampling reference image. Undersampled SWI images were obtained by retrospective undersampling of reference fully sampled images, and the undersampling multiple was five times which could save 80% of the scanning time, then the complex-valued convolutional neural network (ComplexNet) was used to develop reconstruct fast SWI. Interclass correlation coefficient (ICC) or Kappa tests were used to compare the consistency of image quality and the diagnostic consistency for the presence of susceptibility vessel sign (SVS), cerebral microbleeds and asymmetry of cerebral deep medullary veins (DMVs) in AIS patient on fully sampled SWI and fast SWI based on ComplexNet.Results:In test set, score of image quality was 4.5±0.6 for fully sampled SWI image and 4.6±0.7 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.86, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.79, P<0.05), microbleeds (Kappa=0.86, P<0.05), and DMVs asymmetry (Kappa=0.82, P<0.05) in AIS patients. In the external validation set, score of image quality was 4.1±1.0 for fully sampled SWI image and 4.0±0.9 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.97, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.74, P<0.05), microbleeds (Kappa=0.83, P<0.05), and DMVs asymmetry (Kappa=0.74, P<0.05) in AIS patients. Conclusions:Deep learning techniques can significantly accelerate the speed of SWI, and the consistency of image quality and detected AIS signs between fast SWI based on ComplexNet and fully sampled SWI is good. The fast SWI based on ComplexNet can be applied to the radiographic assessment of clinical AIS patients
6.Quality Control Test of Transcranial MRI-guided Focused Ultrasound Treatment System before Surgery.
Xiangbing BIAN ; Qin QIN ; Xingwen ZHANG ; Yeqing QI ; Dekang ZHANG ; Shuai ZHANG
Chinese Journal of Medical Instrumentation 2021;45(3):340-343
OBJECTIVE:
To investigate the pre-treatment preventive maintenance and quality control procedure of MRI system and transcranial MRI-guided focused ultrasound (TcMRgFUS) treatment system by monitoring quality control of these two systems.
METHODS:
The general performance index and image quality control index of MRI system, as well as the quality assurance program of TcMRgFUS EXABLATE 4000 system were tested and recorded.
RESULTS:
The general performance index and image quality control index of MRI system met requirements.
CONCLUSIONS
Through system detection, the system performance could be monitored, ensuring the accuracy and safety of surgery.
Hyperthermia, Induced
;
Magnetic Resonance Imaging
;
Phantoms, Imaging
;
Quality Control
7.Genome mining combined metabolic shunting and OSMAC strategy of an endophytic fungus leads to the production of diverse natural products.
Qian WEI ; Jian BAI ; Daojiang YAN ; Xiuqi BAO ; Wenting LI ; Bingyu LIU ; Dan ZHANG ; Xiangbing QI ; Dequan YU ; Youcai HU
Acta Pharmaceutica Sinica B 2021;11(2):572-587
Endophytic fungi are promising producers of bioactive small molecules. Bioinformatic analysis of the genome of an endophytic fungus
8.Clinical application of orbicularis flap for eyelid groove deformity
Benshou ZHANG ; Xiangbing SHUI ; Hui CHU ; Zengnan LI ; Chao XIE ; Zhijiu XU
Chinese Journal of Plastic Surgery 2016;32(2):122-125
Objective To discuss the correction of lower baggy eyelid with severe tear trough and eyelid sulcus (groove deformity) and its therapeutic effect.Methods Through incision at the lower eyelid margin,the dissection was performed at the deep surface of the orbicularis muscle to expose the orbital septum and inferior orbital rim periosteum.The orbital fat which was released from orbital septum was repositioned at the inferior orbital rim and fixed on periosteum.If the depression was not completely corrected,the extra orbicularis fixed with periosteum.If the depression was not completely corrected,the extra orbicularis muscle was designed as muscle flap with interior pedicle to further correct the groove deformity.Results 60 cases were treated with no depression or unsmooth deformity.All the cases were followed up for 3-12 months with satisfactory aesthetic effect.Conclusions Orbicularis flap combined with orbital fat reposition is a simple and effective method for correction of tear trough and eyelid sulcus deformity.
9.Clinical study of five combined operation for anus reconstruction
Benshou ZHANG ; Lei YAN ; Xiangbing SHUI ; Qiang LI ; Liangbiao XU ; Zhigang YANG ; Zihao LIN
Chinese Journal of Plastic Surgery 2016;32(6):429-431
Objective To study the effect of five combined operation for anus reconstruction after Miles operation in patients with lower colorectal cancer.Methods 60 patients with lower colorectal cancers received Miles operation,followed by five combined operation for anus reconstruction (internal and external anal sphincter,rectal flap,rectal angle,anus perineal reconstruction).Results 5-6 days after operation,all cases had desire to excretion.2-3 weeks lateral,all cases desired to control excretion and excreted 1 or 2 times per-day.Internal rectum testing showed the static pressure in anus,the constrictive pressure,and the static pressure in rectum were all normal.The survival rate of patients over 5 years was beyond 88%.Conclusions It suggests that five combined operation for anus reconstruction after Miles operation could avoid man-made anus on abdomen.It can improve the patients' life quality,long-term survival rate.And it's also economical method for patients.
10.Clinical application of orbicularis flap for eyelid groove deformity
Benshou ZHANG ; Xiangbing SHUI ; Hui CHU ; Zengnan LI ; Chao XIE ; Zhijiu XU
Chinese Journal of Plastic Surgery 2016;32(2):122-125
Objective To discuss the correction of lower baggy eyelid with severe tear trough and eyelid sulcus (groove deformity) and its therapeutic effect.Methods Through incision at the lower eyelid margin,the dissection was performed at the deep surface of the orbicularis muscle to expose the orbital septum and inferior orbital rim periosteum.The orbital fat which was released from orbital septum was repositioned at the inferior orbital rim and fixed on periosteum.If the depression was not completely corrected,the extra orbicularis fixed with periosteum.If the depression was not completely corrected,the extra orbicularis muscle was designed as muscle flap with interior pedicle to further correct the groove deformity.Results 60 cases were treated with no depression or unsmooth deformity.All the cases were followed up for 3-12 months with satisfactory aesthetic effect.Conclusions Orbicularis flap combined with orbital fat reposition is a simple and effective method for correction of tear trough and eyelid sulcus deformity.

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