1.Enzyme-directed Immobilization Strategies for Biosensor Applications
Xing-Bao WANG ; Yao-Hong MA ; Yun-Long XUE ; Xiao-Zhen HUANG ; Yue SHAO ; Yi YU ; Bing-Lian WANG ; Qing-Ai LIU ; Li-He ZHANG ; Wei-Li GONG
Progress in Biochemistry and Biophysics 2025;52(2):374-394
Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.
2.Identification of GSK3 family and regulatory effects of brassinolide on growth and development of Nardostachys jatamansi.
Yu-Yan LEI ; Zheng MA ; Jing WEI ; Wen-Bing LI ; Ying LI ; Zheng-Ming YANG ; Shao-Shan ZHANG ; Jing-Qiu FENG ; Hua-Chun SHENG ; Yuan LIU
China Journal of Chinese Materia Medica 2025;50(2):395-403
This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism*
;
Steroids, Heterocyclic/metabolism*
;
Gene Expression Regulation, Plant/drug effects*
;
Plant Proteins/metabolism*
;
Phylogeny
;
Nardostachys/metabolism*
;
Plant Growth Regulators/pharmacology*
;
Plant Roots/drug effects*
3.Air Pollution and Cardiac Biomarkers in Heart Failure: A Scoping Review.
Gang LI ; Yan Hui JIA ; Yun Shang CUI ; Shao Wei WU ; Tong Yu MA ; Yun Xing JIANG ; Hong Bing XU ; Yu Hui ZHANG ; Mary A FOX
Biomedical and Environmental Sciences 2025;38(11):1430-1443
Ambient air pollution is increasingly being recognized as a risk factor for heart failure; however, its effects on cardiac biomarkers remain unclear. This scoping review assessed the existing evidence on the association between air pollution and cardiac biomarkers in heart failure, described the key concepts, synthesized data, and identified research gaps. Following the PRISMA-ScR guidelines, PubMed, Embase, Web of Science, and CNKI databases were searched for studies on air pollution, heart failure, and biomarkers. A total of 765 records were screened, and 81 full texts were assessed for eligibility, resulting in 15 studies. The results showed that the exposure to particulate matter was associated with elevated N-terminal pro-B-type natriuretic peptide and troponin levels. Several studies have linked particulate matter exposure to a higher cardiovascular risk and heart failure biomarkers. Inflammatory and oxidative stress markers were consistently elevated across studies, supporting the biological relevance of these associations. However, few studies have focused specifically on populations with heart failure or clinically relevant biomarkers, and the evidence for gaseous pollutants remains inconclusive. These findings highlight the need to integrate environmental risk assessment into heart failure care and inform policy efforts to reduce the pollution-related cardiovascular burden. Further research should address these gaps through improved exposure assessments and the integration of mechanistic evidence.
Heart Failure/epidemiology*
;
Biomarkers/metabolism*
;
Humans
;
Air Pollution/adverse effects*
;
Air Pollutants/adverse effects*
;
Particulate Matter/adverse effects*
;
Environmental Exposure
;
Natriuretic Peptide, Brain/blood*
;
Oxidative Stress
;
Troponin/blood*
4.Simulation study of musculoskeletal system of lower limbs based on synergistic effects of stress and electromagnetic fields
Ruo-Bing LIU ; Qi-Lin PEI ; Xi SHAO ; Dan WANG ; Yu-Lan TIAN ; Ze-Dong YAN ; Da JING
Chinese Medical Equipment Journal 2024;45(9):21-26
Objective To apply a COMSOL-based finite element analysis method to investigating the electric field effects produced by the human lower limb musculoskeletal system under the synergistic effects of stress field and electromagnetic field.Methods Firstly,a 3D human body model was constructed by Maxon Cinema 4D R21 software,and then imported into COMSOL 6.1 software in STL format.Secondly,an electromagnetic field intervention and stress loading model for the left lower limb of the human body was designed and constructed,in which 15 Hz quasi-pulse group current signals were used for electromagnetic field excitation and the stress field was realized by applying a vibration load with an average compressive force of about 90 N/cm2 to the left foot of the human body.Finally,the electromagnetic properties of human tissue were simulated by numerical simulation,and then the effects of stress field or elecromagnetic field or combined stress field and electromagnetic field on human bioelectric field were compared.Results Simulation results showed that the electric field intensity peaked at the leg joints under both electromagnetic and stress fields acting alone or synergistically,the bioelectric field intensity generated by the human body was related to the distance from the exogenous excitation loading location,and the electric field generated under synergistic action was equivalent to the linear superposition of the bioelectric field in the tissue induced by the electromagnetic field and the stress field acting alone.Conclusion Data supplement is provided for predicting bioelectric field changes within the musculoskeletal tissue,and theoretical foundation is laid for the development and application of multi-physics field synergistic intervention therapy for treating the disorders of the lower limb musculos-keletal system.[Chinese Medical Equipment Journal,2024,45(9):21-26]
5.Left Ventricle Longitudinal Strain Parameters Are Effective for Differentiating Cardiac Amyloidosis from Primary Hypertensive Left Ventricular Hypertrophy
Ri-qing FENG ; Yuan-li MENG ; Ying-mei LIU ; Qiong QIU ; Shao-xin ZHENG ; Bing-qing DENG ; Yu-lin WEI
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):1046-1052
ObjectiveTo clarify the value of the left ventricular longitudinal strain(LVLS)parameters in patients with cardiac amyloidosis (CA) and primary hypertension with left ventricular hypertrophy (HLVH). MethodsForty-one patients confirmed with CA were selected and assigned to CA with hypertension group (n =14) and pure CA group (n=27) based on the initial diagnosis with or without hypertension. Twenty patients with primary hypertension-induced left ventricular hypertrophy (HLVH group) and twenty healthy controls were also selected, matching for gender, age, and body surface area. Clinical data, conventional echocardiography parameters were collected and LVLS parameters were measured. Within-group variations were compared among the four groups, and pairwise comparisons were conducted between groups. The sensitivity and specificity of each parameter in predicting CA were judged by the receiver operator characteristic (ROC) curvy in CA and HLVH patients with left ventricular ejection fraction (LVEF) preserved. ResultsAmong the conventional echocardiography parameters, LVEF and left ventricular end-diastolic diameter (LVEDD) were lower in the CA with hypertension group and pure CA group compared with the higher values in the HLVH group and control group. Whereas, left ventricular posterior wall thickness (LVPWT), relative wall thickness (RWT), and average E/e' were higher in the two CA groups compared with the HLVH group (all P<0.05).Among the LVLS parameters, Global longitudinal strain (GLS) was the worst in the CA with hypertension group so as pure CA group, modest in the HLVH group, and highest in the control group. On the contrary, relative longitudinal strain and ejection fraction strain ratio (EFSR) were the highest in the CA with hypertension group so as to pure CA group, modest in the HLVH group, and lowest in the control group (all P<0.05). ROC analysis showed that when LVEF was preserved, the absolute value of GLS less than 14.35% and EFSR higher than 4.28 could effectively distinguish CA from HLVH (all AUCs>0.9,all P<0.05); meanwhile GLS showed high sensitivity(100%) and EFSR showed great specificity(95%). There were not statistically significance in any parameter between CA with hypertension group and pure CA group(all P>0.05). ConclusionWhether CA was complicated with hypertension or not, there were statistically significance among routine echocardiography and LVLS parameters compared with HLVH. In particular, GLS and EFSR are accurate in predicting CA in patients with myocardial hypertrophy and preserved LVEF.
6.Second metabolites comparative analysis of Codonopsis pilosula (Franch.) Nannf. from different origins based on extensively targeted metabolomics
Ling-yu LI ; De-fu WANG ; Zhen-fang LI ; Shao-fei SHEN ; Hong-ling TIAN ; Yan-bing NIU
Acta Pharmaceutica Sinica 2023;58(11):3421-3427
We performed an extensively targeting metabolomic detecting using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to compare the secondary metabolites in Dang shen [
7.HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems.
Ping LI ; Ying WU ; Yan XIE ; Feng CHEN ; Shao qiang CHEN ; Yun Hao LI ; Qing Qing LU ; Jing LI ; Yong Wei LI ; Dong Xu PEI ; Ya Jun CHEN ; Hui CHEN ; Yan LI ; Wei WANG ; Hai WANG ; He Tao YU ; Zhu BA ; De CHENG ; Le Ping NING ; Chang Liang LUO ; Xiao Song QIN ; Jin ZHANG ; Ning WU ; Hui Jun XIE ; Jina Hua PAN ; Jian SHUI ; Jian WANG ; Jun Ping YANG ; Xing Hui LIU ; Feng Xia XU ; Lei YANG ; Li Yi HU ; Qun ZHANG ; Biao LI ; Qing Lin LIU ; Man ZHANG ; Shou Jun SHEN ; Min Min JIANG ; Yong WU ; Jin Wei HU ; Shuang Quan LIU ; Da Yong GU ; Xiao Bing XIE
Chinese Journal of Preventive Medicine 2023;57(7):1047-1058
Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy
;
Child
;
Humans
;
Female
;
Glycated Hemoglobin
;
Cohort Studies
;
Diabetes Mellitus/diagnosis*
;
Sensitivity and Specificity
;
ROC Curve
8.Association between muscle mass and quality of life in Shaanxi adults.
Zi Ping WANG ; Hui JING ; Yu Xin TENG ; Yan HUANG ; Samuel CHACHA ; Ye Zhou LIU ; Bin Yan ZHANG ; Yuan SHEN ; Qiang LI ; Bai Bing MI ; Jiao Mei YANG ; Hong YAN ; Shao Nong DANG
Chinese Journal of Epidemiology 2023;44(6):877-884
Objective: To investigate the association between muscle mass and quality of life in adults in Shaanxi adults. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. The participants' quality of life, including physical component summary (PCS) and mental component summary (MCS), was assessed by the 12-Item Short Form Survey, and the Body Fat Determination System measured muscle mass. A logistic regression model with adjustment for confounding factors was established to analyze the association between muscle mass and quality of life in different genders. Further, sensitivity and subgroup analyses were conducted to explore its stability. Finally, a restricted cubic spline was employed to investigate the dose-response relationship between muscle mass and quality of life in different genders. Results: A total of 20 595 participants were included, with an average age of 55.0, and 33.4% were male. After controlling for potential confounders, compared with the Q1 group, the risk of low PCS was reduced by 20.6% (OR=0.794, 95%CI: 0.681-0.925) and the risk of low MCS was lower reduced by 20.1% (OR=0.799, 95%CI: 0.689-0.926) in female Q5 groups. Compared with the Q1 group, the risk of low PCS was reduced by 24.4% (OR=0.756, 95%CI: 0.644-0.888) in the male Q2 group. However, no significant association between muscle mass and MCS in males has been found. In females, restricted cubic spline analysis showed a significant linear dose-response relationship between muscle mass and PCS and MCS. Conclusions: There is a positive association between muscle mass and quality of life in Shaanxi adults, especially females. With the increase in muscle mass, the physical and mental functions of the population continue to improve.
Humans
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Female
;
Adult
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Male
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Quality of Life
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Cohort Studies
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Adipose Tissue
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China
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Muscles
9.Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study.
Yao Chen LOU ; Shuang ZHOU ; Jiong Bo LIAO ; Wen Yu SHAO ; Ying Ying HU ; Cheng Cheng NING ; Qian WANG ; Yierfulati GULINAZI ; Bing Yi YANG ; Ya Li CHENG ; Peng Fei WU ; Qin ZHU ; Xian Rong ZHOU ; Wei Wei SHAN ; Xiao Jun CHEN
Chinese Journal of Obstetrics and Gynecology 2023;58(7):526-535
Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female
;
Humans
;
Adult
;
Medroxyprogesterone Acetate/adverse effects*
;
Endometrial Hyperplasia/pathology*
;
Dydrogesterone/adverse effects*
;
Hyperplasia
;
Prospective Studies
10.Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients.
Jia Xin LI ; Lin SUN ; Shuai ZHAO ; Bing SHAO ; Yu Hong GUO ; Shuai CHEN ; Han LIANG ; Y SUN
Chinese Journal of Gastrointestinal Surgery 2023;26(4):346-356
Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.
Male
;
Humans
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Gastrointestinal Stromal Tumors/surgery*
;
Retrospective Studies
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Ki-67 Antigen
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Stomach Neoplasms/pathology*
;
Prognosis
;
Mutation
;
Intestines/pathology*
;
Proto-Oncogene Proteins c-kit/genetics*
;
Receptor, Platelet-Derived Growth Factor alpha/genetics*

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