Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of 2785 person-years, resulting in an incidence density of 8007.18 per 100000 person-years, an average age of onset of (35.90±8.22) years, and an average working age of onset of (2.69±1.97) years. The incidence density in the exposure group was 128.71% higher than that in the control group, and the risk of hypertension in the exposure group was 2.115 times that of the control group. The risk of hypertension was 2.199 times higher for men than for women, 1.344 times higher for those aged 30 and above than for those under 30, 1.546 times higher for smokers than for non-smokers, and 1.750 times higher for drinking workers than for non-drinking ones. The results of Cox proportional hazards regression modeling indicated that the hazard ratio (95%CI) of hypertension among the employees exposed to dust, noise, and carbon monoxide was 2.254 (1.703, 2.982), 1.594 (1.107, 2.295), and 1.567 (1.079, 2.274), respectively, when different covariates (gender, age, smoking, and alcohol consumption) were included. The results of Log-rank test showed that there were statistically significant differences in the distribution of disease-free survival between the exposure group and the control group (P<0.05). Conclusion Occupational exposures to dust, noise, and carbon monoxide may increase the risk of hypertension among calcium carbide plant workers.

OBJECTIVE: The triply periodic minimal surface (TPMS) Gyroid porous scaffolds were built with identical porosity while varying pore sizes were used by fluid mechanics finite element analysis (FEA) to simulate the in vivo microenvironment. The effects of scaffolds with different pore sizes on cell adhesion, proliferation, and osteogenic differentiation were evaluated through calculating fluid velocity, wall shear stress, and permeability in the scaffolds. METHODS: Three types of gyroid porous scaffolds, with pore sizes of 400, 600 and 800 μm, were established by nTopology software. Each scaffold had dimensions of 10 mm × 10 mm × 10 mm and isotropic internal structures. The models were imported to the ANSYS 2022R1 software, and meshed into over 3 million unstructured tetrahedral elements. Boun- dary conditions were set with inlet flow velocities of 0.01, 0.1, and 1 mm/s, and outlet pressure of 0 Pa. Pressure, velocity, and wall shear stress were calculated as fluid flowed through the scaffolds using the Navier-Stokes equations. At the same time, permeability was determined based on Darcy' s law. The compressive strength of scaffolds with different pore sizes was evaluated by ANSYS 2022R1 Static structural analysis. RESULTS: A linear relationship was observed between the wall shear stress and fluid velocity at inlet flow rates of 0.01, 0.1 and 1 mm/s, with increasing velocity leading to higher wall shear stress. At the flow velocity of 0.1 mm/s, the initial pressures of scaffolds with pore sizes of 400, 600 and 800 μm were 0.272, 0.083 and 0.079 Pa, respectively. The fluid pressures were gradually decreased across the scaffolds. The average flow velocities were 0.093, 0.078 and 0.070 mm/s, the average wall shear stresses 2.955, 1.343 and 1.706 mPa, permeabilities values 0.54×10^-8 1.80×10^-8 and 1.89×10^-8 m² in the scaffolds with pore sizes of 400, 600 and 800 μm. The scaffold surface area proportions according with optimal wall shear stress range for cell growth and osteogenic differentiation were calcula-ted, which was highest in the 600 μm scaffold (27.65%), followed by the 800 μm scaffold (17.30%) and the 400 μm scaffold (1.95%). The compressive strengths of the scaffolds were 23, 26 and 34 MPa for the 400, 600 and 800 μm pore sizes. CONCLUSION The uniform stress distributions appeared in all gyroid scaffold types under compressive stress. The permeabilities of scaffolds with pore sizes of 600 and 800 μm were significantly higher than the 400 μm. The average wall shear stress in the scaffold of 600 μm was the lowest, and the scaffold surface area proportion for cell growth and osteogenic differentiation the largest, indicating that it might be the most favorable design for supporting these cellular activities.
Tissue Scaffolds/chemistry* ; Porosity ; Finite Element Analysis ; Osteogenesis ; Cell Differentiation ; Cell Proliferation ; Tissue Engineering/methods* ; Hydrodynamics ; Humans ; Stress, Mechanical ; Cell Adhesion

Objective: The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse.We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis. Methods: Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging. Results: There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences.Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC. Conclusion Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.

Objective:To investigate the 10-year outcome and prognostic factors of laparo-scopic D 2 radical distal gastrectomy for locally advanced gastric cancer. Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 652 patients with locally advanced gastric cancer who were admitted to 16 hospitals from the multicenter database of laparoscopic gastric cancer surgery in the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group, including 214 cases in the First Affiliated Hospital of Army Medical University, 191 cases in Fujian Medical University Union Hospital, 52 cases in Nanfang Hospital of Southern Medical University, 49 cases in West China Hospital of Sichuan University, 43 cases in Xijing Hospital of Air Force Medical University, 25 cases in Jiangsu Province Hospital of Chinese Medicine, 14 cases in the First Medical Center of the Chinese PLA General Hospital, 12 cases in No.989 Hospital of PLA, 12 cases in the Third Affiliated Hospital of Sun Yat-Sen University, 10 cases in the First Affiliated Hospital of Nanchang University, 9 cases in the First People's Hospital of Foshan, 7 cases in Zhujiang Hospital of Southern Medical University, 7 cases in Fujian Medical University Cancer Hospital, 3 cases in Zhongshan Hospital of Fudan University, 2 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2 cases in Peking University Cancer Hospital & Institute, from February 2004 to December 2010 were collected. There were 442 males and 210 females, aged (57±12)years. All patients underwent laparoscopic D 2 radical distal gastrectomy. Observation indicators: (1) surgical situations; (2) postoperative pathological examination; (3) postoperative recovery and complications; (4) follow-up; (5) prognostic factors analysis. Follow-up was conducted by outpatient examination and telephone interview to detect the tumor recurrence and metastasis, postoperative survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percen-tages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-Rank test was used for survival analysis. Univariate and multivariate analyses were analyzed using the COX hazard regression model. Results:(1) Surgical situations: among 652 patients, 617 cases underwent D 2 lymph node dissection and 35 cases underwent D 2+ lymph node dissection. There were 348 cases with Billroth Ⅱ anastomosis, 218 cases with Billroth Ⅰ anastomosis, 25 cases with Roux-en-Y anastomosis and 61 cases with other digestive tract reconstruction methods. Twelve patients had combined visceral resection. There were 569 patients with intraoperative blood transfusion and 83 cases without blood transfusion. The operation time of 652 patients was 187(155,240)minutes and volume of intraoperative blood loss was 100(50,150)mL. (2) Postoperative pathological examina-tion: the maximum diameter of tumor was (4.5±2.0)cm of 652 patients. The number of lymph node dissected of 652 patients was 26(19,35), in which the number of lymph node dissected was >15 of 570 cases and ≤15 of 82 cases. The number of metastatic lymph node was 4(1,9). The proximal tumor margin was (4.8±1.6)cm and the distal tumor margin was (4.5±1.5)cm. Among 652 patients, 255 cases were classified as Borrmann type Ⅰ-Ⅱ, 334 cases were classified as Borrmann type Ⅲ-Ⅳ, and 63 cases had missing Borrmann classification data. The degree of tumor differentiation was high or medium in 171 cases, low or undifferentiated in 430 cases, and the tumor differentiation data was missing in 51 cases. There were 123, 253 and 276 cases in pathological stage T2, T3 and T4a, respectively. There were 116, 131, 214 and 191 cases in pathological stage N0, N1, N2 and N3, respectively. There were 260 and 392 cases in pathological TNM stage Ⅱ and Ⅲ, respectively. (3) Postoperative recovery and complications: the time to postoperative first out-of-bed activities, time to postoperative first flatus, time to the initial liquid food intake, duration of postoperative hospital stay of 652 patients were 3(2,4)days, 4(3,5)days, 5(4,6)days, 10(9,13)days, respectively. Among 652 patients, 69 cases had postoperative complications. Clavien-Dindo grade Ⅰ-Ⅱ, grade Ⅲa, grade Ⅲb, and grade Ⅳa complications occurred in 60, 3, 5 and 1 cases, respectively (some patients could have multiple complications). The duodenal stump leakage was the most common surgical complication, with the incidence of 3.07%(20/652). Respiratory complication was the most common systemic complication, with the incidence of 2.91%(19/652). All the 69 patients were recovered and discharged successfully after treatment. (4) Follow-up: 652 patients were followed up for 110-193 months, with a median follow-up time of 124 months. There were 298 cases with postoperative recurrence and metastasis. Of the 255 patients with the time to postoperative recurrence and metastasis ≤5 years, there were 21 cases with distant metastasis, 69 cases with peritoneal metastasis, 37 cases with local recurrence, 52 cases with multiple recurrence and metastasis, 76 cases with recurrence and metastasis at other locations. The above indicators were 5, 9, 10, 4, 15 of the 43 patients with the time to postoperative recurrence and metastasis >5 years. There was no significant difference in the type of recurrence and metastasis between them ( χ2=5.52, P>0.05). Cases in pathological TNM stage Ⅱ and Ⅲ were 62 and 193 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 23 and 20 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological TNM staging between them ( χ2=15.36, P<0.05). Cases in pathological stage T2, T3, T4a were 42, 95, 118 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 9, 21, 13 of the patients with the time to postoperative recurrence and metastasis >5 years, showing no significant difference in pathological T staging between them ( Z=-1.80, P>0.05). Further analysis showed no significant difference in cases in pathological stage T2 or T3 ( χ2=0.52, 2.08, P>0.05) but a significant difference in cases in pathological stage T4a between them ( χ2=3.84, P<0.05). Cases in pathological stage N0, N1, N2, N3 were 19, 44, 85, 107 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 12, 5, 18, 8 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological N staging between them ( Z=-3.34, P<0.05). Further analysis showed significant differences in cases in pathological stage N0 and N3 ( χ2=16.52, 8.47, P<0.05) but no significant difference in cases in pathological stage N1 or N2 ( χ2=0.85, 1.18, P>0.05). The median overall survival time was 81 months after surgery and 10-year overall survival rate was 46.1% of 652 patients. The 10-year overall survival rates of patients in TNM stage Ⅱ and Ⅲ were 59.6% and 37.5%, respectively, showing a significant difference between them ( χ2=35.29, P<0.05). In further analysis, the 10-year overall survival rates of patients in pathological TNM stage ⅡA, ⅡB, ⅢA, ⅢB and ⅢC were 65.6%, 55.8%, 46.9%, 37.1% and 24.0%, respectively, showing a significant difference between them ( χ2=55.06, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage T2, T3 and T4a were 55.2%, 46.5% and 41.5%, respectively, showing a significant difference between them ( χ2=8.39, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage N0, N1, N2 and N3 were 63.7%, 56.2%, 48.5% and 26.4%, respectively, showing a signifi-cant difference between them ( χ2=54.89, P<0.05). (5) Prognostic factors analysis: results of univariate analysis showed that age, maximum diameter of tumor, degree of tumor differentiation as low or undifferentiated, pathological TNM staging, pathological T staging, pathological stage N2 or N3, post-operative chemotherapy were related factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrectomy ( hazard ratio=1.45, 1.64, 1.37, 2.05, 1.30, 1.68, 3.08, 0.56, 95% confidence interval as 1.15-1.84, 1.32-2.03, 1.05-1.77, 1.62-2.59, 1.05-1.61, 1.17-2.42, 2.15-4.41, 0.44-0.70, P<0.05). Results of multivariate analysis showed that maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ were independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrectomy ( hazard ratio=1.48,1.44, 1.81, 95% confidence interval as 1.19-1.84, 1.11-1.88, 1.42-2.30, P<0.05) and postoperative chemotherapy was a independent protective factor for the 10-year overall survi-val rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrec-tomy ( hazard ratio=0.57, 95% confidence interval as 045-0.73, P<0.05). Conclusions:Laparoscopic assisted D 2 radical distal gastrectomy for locally advanced gastric cancer has satisfactory 10-year oncologic outcomes. A high proportion of patients in pathological TNM stage Ⅲ, pathological stage T4a, pathological stage N3 have the time to postoperative recurrence and metastasis ≤5 years, whereas a high proportion of patients in pathological TNM stage Ⅱ or pathological stage N0 have the time to postoperative recurrence and metastasis >5 years. Maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ are independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D 2 radical distal gastrectomy. Postoperative chemotherapy is a independent protective factor for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D 2 radical distal gastrectomy.

Objective:To examine the survival rates and clinical characteristics of people with newly discovered non-M 3 acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods:From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M 3 AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results:① The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1 +) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1 -) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . ②WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1 - patients, while complete response after the first round of treatment (CR 1) was lower ( P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1 + patients were higher than those in ASXL1 - patients ( P<0.05) . In the young group, the WBC of ASXL1 + patients was higher than that of ASXL1 - patients ( z=-2.314, P=0.021) . ③IDH2 mutation and ASXL1 mutation was related ( P=0.018, r=0.34) . In ASXL1 + patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients ( P<0.05) . ④The overall survival (OS) and progression-free survival (PFS) of ASXL1 + patients were shorter than those of ASXL1 - patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1 + patients, according to multivariate analysis ( P<0.05) . Conclusion:ASXL1-mutated non-M 3 AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR 1 rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.

Based on the clinical application data of medical X-ray computed tomography (CT) in the Shanghai Sixth People's Hospital, this study transformed it into the product reliability index requirements, and took the mechanical representative component-examination table (hereinafter referred to as "patient table") and the electronic representative component-DCB (data control board) as examples. Based on the relationship between failure characteristics and clinical application data, a complete set of closed-loop implementation methods from reliability index requirements to reliability design and verification are discussed.
China ; Humans ; Reproducibility of Results ; Tomography, X-Ray Computed

Combined with the clinical use condition of MR in use in Shanghai Sixth People's Hospital, MR components are divided into scanning type I and scanning type II. At the same time, combined with the main loss force of MR components, the research divides MR components into dynamic components and electric thermal components. In this study, a complete set of MR system reliability indexes and implementation methods are given, including system reliability index determination, system reliability allocation, component reliability index realization, system reliability prediction and system reliability verification. At the same time, this study also gives the methods of reliability prediction and reliability verification, and gives the MTBF calculation method of MR system based on clinical use data statistics.
China ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Reproducibility of Results

Objective:To investigate protective effect of Pinus massoniana needle extract (PMNE) against oxidative stress in human dermal papilla cells (HDPC) , and to explore its mechanisms. Methods:As research objects, some cultured HDPC were treated with H 2O 2 at different concentrations of 0 (control group) , 0.1, 0.2, 0.4, 0.8 and 1.0 mmol/L, in order to establish the optimal condition for in vitro oxidative stress in HDPC; some other HDPC were transfected with nuclear factor-erythroid 2-related factor 2 (Nrf2) specific small interfering RNAs (siRNA1, siRNA2, siRNA3) or a Nrf2-overexpressing plasmid (pCMV6-XL5-Nrf2) , the HDPC transfected with a scrambled-siRNA and an empty plasmid pCMV6-XL5 served as the control siRNA group and control plasmid group respectively, and HDPC subjected to conventional culture served as the blank group; after the above treatment, real-time fluorescence-based quantitative PCR and Western blot analysis were performed to determine Nrf2 mRNA and protein expression, respectively; cell viability and apoptosis were detected in the above transfected cells after the treatment with H 2O 2 at an optimal concentration. In the subsequent experiment, some HDPC were divided into several groups: control group subjected to conventional culture, dihydrotestosterone group treated with 0.03 μg/ml dihydrotestosterone, proanthocyanidin group treated with 0.03 μg/ml dihydrotestosterone and 6.00 μg/ml proanthocyanidin B2, PMNE groups treated with 0.03 μg/ml dihydrotestosterone and PMNE at different concentrations of 1, 5, 25 and 100 μg/ml; after the above treatment, cell viability and apoptosis were detected, relative fluorescence intensity of intracellular reactive oxygen species (ROS) , malondialdehyde (MDA) content, mRNA and protein expression of Nrf2, quinone oxidoreductase 1 (NQO1) , heme oxygenase 1 (HO-1) , Kelch-like ECH-related protein 1 (Keap1) , transforming growth factor (TGF) -β1, Sma- and Mad-related protein 2/3 (Smad2/3) , phosphorylated Smad2/3 (p-Smad2/3) were determined in HDPC. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference- t test for multiple comparisons. Results:The viability of HDPC ranged from 75% to 85% after the treatment with 0.4 mmol/L H 2O 2, which was selected as the optimal condition for in vitro oxidative stress in HDPC. Compared with the blank group and control siRNA group, the Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups showed significantly decreased Nrf2 mRNA and protein expression (all P < 0.05) , but significantly increased apoptosis rate (Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups, blank group and control group: 12.50% ± 0.05%, 26.07% ± 0.05%, 58.44% ± 1.03%, 10.38% ± 0.64%, 13.05% ± 0.12%, respectively; all P < 0.05) . Nrf2 protein expression was the lowest in the Nrf2-siRNA2 group, so Nrf2-siRNA2 was selected as the optimal interfering fragment for subsequent experiments. Compared with the blank group and control plasmid group, the Nrf2 overexpression group showed significantly increased Nrf2 mRNA and protein expression (both P < 0.05) , but a significantly decreased apoptosis rate (all P < 0.05) . After the treatment with 0.4 mmol/L H 2O 2, the Nrf2 overexpression group showed a significantly decreased apoptosis rate, but significantly increased cell viability compared with the empty vector group ( t = 3.66, 40.40, respectively, both P < 0.001) ; the Nrf2-siRNA2 group showed a significantly increased apoptosis rate, but significantly decreased cell viability compared with the control group ( t = 13.13, 67.37, respectively, both P < 0.001) . In the PMNE treatment experiment, the proanthocyanidin group and PMNE groups showed significantly increased cell viability, but significantly decreased apoptosis rates compared with the dihydrotestosterone group (all P < 0.01) ; proanthocyanidin and PMNE at different concentrations could significantly inhibit dihydrotestosterone-induced overexpression of ROS and MDA in HDPC (all P < 0.01) ; the protein expression of Nrf2, NQO1 and HO-1 was significantly higher in the proanthocyanidin group, 5-, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) , while the protein expression of Keap1 and TGF-β1, and the Smad2/3 phosphorylation level were significantly lower in the proanthocyanidin group, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) . Conclusion:Nrf2 plays an important role in protecting against oxidative damage in HDPC, and PMNE may exert marked protective effect on HDPC by activating the Nrf2-antioxidant responsive element signaling pathway.

Objective:Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods:A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed.Results:Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades ( P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender ( P=0.010), tumor size ( P=0.042), mitotic count ( P=0.003), and the modified NIH risk stratification ( P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions:Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.

Objective:Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods:A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed.Results:Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades ( P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender ( P=0.010), tumor size ( P=0.042), mitotic count ( P=0.003), and the modified NIH risk stratification ( P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions:Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.