Background and Aims:Gastric cancer is a common and highly lethal malignancy of the digestive system.The efficacy of current treatment strategies remains limited,highlighting the urgent need to identify novel therapeutic targets.This study employed a Mendelian randomization(MR)approach to integrate GWAS data with pQTL data,aiming to systematically identify and validate plasma proteins that are causally associated with gastric cancer,thereby providing a theoretical basis for targeted therapy.Methods:A two-sample Mendelian randomization analysis was conducted using GWAS data on gastric cancer and plasma pQTL datasets to infer causal relationships.External independent datasets were used for validation.Multi-dimensional sensitivity analyses-including reverse causality testing,Bayesian colocalization,and phenome-wide scans-were performed to ensure the robustness of the findings.Protein-protein interaction networks were constructed via the STRING database to elucidate the biological pathways of candidate proteins,and the DrugBank database was utilized to predict potential therapeutic agents.Results:A total of 16 plasma proteins were initially identified as causally associated with the risk of gastric cancer.After external validation and sensitivity analyses,ICAM2,IGF1R,LIFR,and MET were confirmed as key candidate targets.Drug database analysis indicated that dalotuzumab(targeting IGF1R)and efalizumab(potentially modulating the ICAM2 pathway)may have therapeutic potential.Conclusion:Through a multi-omics Mendelian randomization framework,this study systematically identified four plasma proteins-ICAM2,IGF1R,LIFR,and MET-that exhibit stable causal associations with gastric cancer.These targets offer novel insights into the molecular pathogenesis of gastric cancer and provide a theoretical foundation for developing targeted drugs and personalized treatment strategies.

Background and Aims:Gastric cancer is a common and highly lethal malignancy of the digestive system.The efficacy of current treatment strategies remains limited,highlighting the urgent need to identify novel therapeutic targets.This study employed a Mendelian randomization(MR)approach to integrate GWAS data with pQTL data,aiming to systematically identify and validate plasma proteins that are causally associated with gastric cancer,thereby providing a theoretical basis for targeted therapy.Methods:A two-sample Mendelian randomization analysis was conducted using GWAS data on gastric cancer and plasma pQTL datasets to infer causal relationships.External independent datasets were used for validation.Multi-dimensional sensitivity analyses-including reverse causality testing,Bayesian colocalization,and phenome-wide scans-were performed to ensure the robustness of the findings.Protein-protein interaction networks were constructed via the STRING database to elucidate the biological pathways of candidate proteins,and the DrugBank database was utilized to predict potential therapeutic agents.Results:A total of 16 plasma proteins were initially identified as causally associated with the risk of gastric cancer.After external validation and sensitivity analyses,ICAM2,IGF1R,LIFR,and MET were confirmed as key candidate targets.Drug database analysis indicated that dalotuzumab(targeting IGF1R)and efalizumab(potentially modulating the ICAM2 pathway)may have therapeutic potential.Conclusion:Through a multi-omics Mendelian randomization framework,this study systematically identified four plasma proteins-ICAM2,IGF1R,LIFR,and MET-that exhibit stable causal associations with gastric cancer.These targets offer novel insights into the molecular pathogenesis of gastric cancer and provide a theoretical foundation for developing targeted drugs and personalized treatment strategies.

Objective:To evaluate the left ventricular myocardial strain and mechanical synchrony in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) by two-dimensional speckle tracking imaging (2D-STI) and real-time three-dimensional echocardiography (RT-3DE), and to investigate the value of combined echocadiographic parameters in predication of significant coronary artery stenosis.Methods:A total of 95 patients suspected of NSTE-ACS, definitely planed to run coronary angiography (CAG) within 24-72 hours of admission were recruited in the Department of Cardiology, General Hospital of the Southern Theatre Command, PLA from December 2020 to June 2021. Regular echocardiography exam, 2D-STI and RT-3DE were performed prior to CAG.Global longitudinal peak strain (GLPS), territorial longitudinal peak strain (T RCALPS, T LADLPS, T LCXLPS) were computed by 2D-STI; the maximal difference of time to minimal systolic volume of 16-segments (Tmsv16-Dif), standard deviation of time to minimal systolic volume of 16-segment (Tmsv16-SD) and heart rate adjusted standard deviation of time to minimal systolic volume of 16-segment (Tmsv16-SD/R-R) were obtained by RT-3DE. The patients were divided into two groups according to the degree of coronary stenosis.Significant coronary artery stenosis group was defined as ≥70% of left main or any other main branch luminal narrowing ( n=53), non-significant coronary artery stenosis group was defined as <70% of luminal narrowing ( n=42). The differences of general clinical features, left ventricular strain and mechanical synchronization parameters between the two groups were compared. A binary logistic regression model was established to draw the ROC curve for predicting the severity of coronary stenosis by single and combined ultrasound parameters, and calculate the area under the ROC curve (AUC). Results:Compared with non-significant coronary artery stenosis group, GLPS were significantly reduced, while Tmsv16-SD, Tmsv16-Dif and Tmsv16-SD/R-R were significantly increased in sginificant coronary artery stenosis group (all P<0.05). The AUC of GLPS and Tmsv16-SD, Tmsv16-Dif and Tmsv16-SD/R-R for predicting significant coronary stenosis in suspected NSTE-ACS patients were 0.78, 0.69, 0.71 and 0.67, respectively. The result of joint test analysis for the dignosis of NSTE-ACS suspected significant coronary stenosis were as follows: the specificity of tandem test was 90.5%; the sensitivity of parallel test was 83.0%; the sensitivity, specificity and AUC of GLPS-Tmsv16-Dif joint index prediction test were 90.7%, 60.1% and 0.82 (95% CI=0.73-0.89) with 0.508 as Youden index. Conclusions:NSTE-ACS suspected patients with significant coronary stenosis are often accompanied by impaired left ventricular myocardial strain and mechanical dyssynchrony. A simple combination of left ventricular myocardial strain and contractility synchronization improves noninvasive prediction of high-risk coronary artery stenosis in suspected NSTE-ACS, which maybe helpful for screening patients requiring invasive examination.

Objective:To analyze the MRI features of hepatic epithelioid hemangioendothelioma (HEHE).Methods:The data of patients with HEHE managed in the Wenzhou People's Hospital of Zhejiang Province and the First Affiliated Hospital of Wenzhou Medical University from April 2000 to April 2019 were retrospectively analyzed. Among the 26 patients with HEHE, there were 12 males and 14 females, aged from 23 to 65 years (average 44.4 years). The quantity, size, shape and type of the lesions were observed and the MRI features were analyzed.Results:Of the 382 nodules detected by MRI in the 26 patients, the size varied from 0.5cm to 12.0 cm, with 16 nodules being more than 5.0 cm in diameter (average of 2.2 cm). Four patients with a single nodular type presented with low signal on T 1 weighted imaging (T 1WI), high signal on T 2 weighted imaging (T 2WI), high signal on diffused weighted imaging (DWI), and high central signal and low peripheral annular signal on apparent diffusion coefficient (ADC). After enhancement, the lesions presented with annular centripetal enhancement or continuous annular enhancement. Fourteen patients with multiple nodules had a total of 147 lesions, presenting with low signal on T 1WI, high signal on T 2WI, high signal on DWI, and high central signal and low peripheral annular signal on ADC. After enhancement, the lesions presented with annular centripetal enhancement and continuous annular enhancement. There were 24 lesions in 6 patients who had a " double-ring sign" , 21 lesions in 7 patients who had a capsule " shriveled sign" , 16 lesions in 7 patients who had a " lollipop sign" and 18 lesions in 5 patients who had an " intravascular sign" . There were 231 lesions in 8 patients of the fusion type. The lesions showed low signal on T 1WI, high signal on T 2WI , high signal on DWI, and high central signal and low peripheral signal on ADC. After enhancement, the lesions presented with flocculent or annular centripetal enhancement. In 8 patients, 87 lesions had a " target sign" , 55 lesions had a " lollipop sign" and 42 lesions had a capsule " shriveled sign" , and 36 lesions in 5 patients had an " intravascular sign" . Conclusion:MRI signs of HEHE have certain characteristics, such as lesions being distributed near the capsule, and fusing with each other; a " target sign" on T 2WI; a capsule " shriveled sign " ; and a " double-ring sign" , a " lollipop sign" , an " intravascular sign" in the portal phase. These features are helpful in diagnosing HEHE.

Objective:To observe the changes of LHX4 and DIS3L mRNA and protein expression in Nthy-ori-3-1 cells after the treatment of thyroid disruptor p, p'-DDE. Methods:Nthy-ori-3-1 cells in logarithmic growth phase were treated with 0, 0.5, 1.0, 2.0 and 5.0 μg/ml p, p'-DDE solution. The growth state and morphology of the cells were observed by microscope. The mRNA levels of LHX4 and DIS3L were detected by real-time fluorescent quantitative PCR, and the protein expression levels of LHX4 and DIS3L were detected by Western blot. Results:when the concentrations of p, p'-DDE were 0, 0.5, 1.0 and 2.0 μg/ml, Nthy-ori-3-1 cells grew normally. There were 33 differential genes in 2.0 μg/ml group, among which 13 genes were down regulated and 20 genes were up-regulated. Compared with the control group, the protein expression levels of LHX4 and DIS3L in 1.0 and 2.0 μg/ml groups were significantly decreased ( P<0.05) , and the relative expression levels of LHX4 and DIS3L protein mRNA in 1.0 μg/ml group were significantly decreased ( P<0.05) . Conclusion:p, p'-DDE can affect the protein expression of LHX4 and dis3l in nthy-ori-3-1 cells.

Objective:To observe the changes of LHX4 and DIS3L mRNA and protein expression in Nthy-ori-3-1 cells after the treatment of thyroid disruptor p, p'-DDE. Methods:Nthy-ori-3-1 cells in logarithmic growth phase were treated with 0, 0.5, 1.0, 2.0 and 5.0 μg/ml p, p'-DDE solution. The growth state and morphology of the cells were observed by microscope. The mRNA levels of LHX4 and DIS3L were detected by real-time fluorescent quantitative PCR, and the protein expression levels of LHX4 and DIS3L were detected by Western blot. Results:when the concentrations of p, p'-DDE were 0, 0.5, 1.0 and 2.0 μg/ml, Nthy-ori-3-1 cells grew normally. There were 33 differential genes in 2.0 μg/ml group, among which 13 genes were down regulated and 20 genes were up-regulated. Compared with the control group, the protein expression levels of LHX4 and DIS3L in 1.0 and 2.0 μg/ml groups were significantly decreased ( P<0.05) , and the relative expression levels of LHX4 and DIS3L protein mRNA in 1.0 μg/ml group were significantly decreased ( P<0.05) . Conclusion:p, p'-DDE can affect the protein expression of LHX4 and dis3l in nthy-ori-3-1 cells.

Objective To observe the clinical features of atrial fibrillation (AF) patients, and to explore the correlation between the routine detection index and the new-onset AF and to find out risk factors for new AF in critically ill patients. Methods A prospective observational study was conducted. The patients with AF admitted to intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from March 2016 to June 2017 were enrolled. The patients were divided into new-onset AF group and past-existed AF group according to their past history of AF (including persistent AF, paroxysmal AF or permanent AF). In addition, patients in ICU without history of AF and new-onset AF were selected as the control group (no AF group). The general epidemiological characteristics of patients in three groups, and the blood biochemical, coagulation and other related indicators at the time of AF occurred (new-onset AF group) or 48 hours after ICU admission (AF group and no AF group) were analyzed; the difference of laboratory indexes between patients in new-onset AF group with AF within 48 hours before occurred and patients in no AF group within 48 hours after admission to ICU was compared. The relationship between each index and new-onset AF were analyzed. Pearson or Spearman rank correlation was used for analysis. Risk factors of new-onset AF were analyzed by Logistic regression analysis. Results 1 673 patients were admitted to ICU, including 179 cases of AF (10.70%), and 106 males and 73 females, with an average age of (71.73±23.22) years. There was 75 new-onset AF (morbidity 4.48%), and had a 28-day mortality of 45.33% (34/75). There were differences in age, previous heart disease and heart failure (HF) among new-onset AF group (n = 75), past-existed AF group (n = 104) and no AF group (n = 75). Compared with other two groups, renal insufficiency rates, troponin, serum sodium, calcium and procalcitonin levels were higher, mechanical ventilation time and the length of ICU stay were significantly prolonged, ICU and hospitalization costs were higher in new-onset AF group. Compared with no AF group, new-onset AF patients with the higher percentage of septic shock, the accumulation of vascular contraction drugs within 24 hours after AF usage were higher, and used more anti-arrhythmic drugs, has higher brain natriuretic peptide (pro-BNP), serum creatinine, blood lactic acid levels, and lower albumin, oxygenation index, and serum potassium levels, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score and 28-day mortality were higher. Correlation analysis showed that age, APACHE Ⅱ score, septic shock, HF, cardiovascular disease, renal insufficiency were positively correlated with new-onset AF (r values were 0.393, 0.270, 0.386, 0.251, 0.194, 0.170;P values were 0.000, 0.001, 0.000, 0.002, 0.017, 0.037, respectively). The age [odds ratio (OR) = 0.962, P = 0.046], basic oxygenation index (OR = 1.005, P = 0.028) and serum potassium levels (OR = 1.638, P = 0.022) were the risk factors for new-onset AF. Conclusions Critical patients with a high incidence of AF, new-onset AF significantly prolong the length of ICU stay; age, APACHE Ⅱ score, septic shock, cardiovascular disease, and renal insufficiency are related to new-onset AF; age, basic oxygenation index and serum potassium levels are risk factors for new-onset AF.

Objective To identify Chinese character writing related cortex (WRC) and its relationship with hand motor cortical areas. Methods Ten native Chinese-speaking, right-hand volunteers were recruited in the study. NTMS mapping was conducted during picture naming task. The WRC were mapped based on nTMS-induced impairment of Chinese character writing. The extent and area of WRC was calculated. The right-hand motor representations were mapped while motor-evoked potentials were produced under nTMS stimulation. EMG data and coordinates of positive stimulus were recorded. The relationship between WRC and hand motor cortex (HMC) was analyzed on the basis of area comparison and distance calculation. Results The cortical areas related to Chinese character writing were mapped successfully in all subjects by nTMS. WRC was primarily centered in left posterior middle frontal gyrus (pMFG) (86%,55/64). The mean WRC area (161.03 mm2 ±62.58mm2) was significantly smaller than the mean HMC area (589.50 mm2±227.34mm2) (P<0.001). The WRC and HMC were not conjoined or overlapped in the dominant hemisphere. The distance between those two was 12.58mm±2.71mm. Conclusions NTMS can provide reliable assistance in mapping WRC areas. The WRC is relatively fixed and centralized in pMFG but is not overlapped with the HMC.

Objective:The implementation of a multidisciplinary team (MDT) approach for palliative treatment of patients with multi-ple primary carcinomas (MPCs) was evaluated in Tianjin Medical University Cancer Institute and Hospital. Methods:A total of 40 pa-tients with MPCs who attended the consultation by MDT in our hospital from January 1, 2014 to April 21, 2016 were analyzed retro-spectively. Clinical data of the 40 cancer patients were reviewed. The essential characteristics and results of MDT treatment decisions were summarized and expected outcomes were evaluated. Results:A total of 40 cases with MPCs were included in MDT assessment, accounting for 6.4%of the 629 patients who were handled by the MDT. A total of 39 MDT decisions were followed up successfully. Among these MDT decisions, 26 (65%) were fully implemented, 7 (17.5%) were partially implemented, and 6 (15.0%) were unimple-mented. Expected outcomes were achieved in 25 (96.2%) patients of the fully implemented concordant group, 4 (57.1%) patients of the partially concordant group, and 1 (16.7%) patient from the unimplemented group. Conclusion:MDT specializing on palliative treat-ment can provide recommendations for standardized individualized comprehensive treatment of patients with MPCs. MDT modality should be further improved and widely used for palliative treatment.

Symptomatic venous thromboembolism (VTE) has a six-to seven-fold risk of occurring in cancer patients compared with non-cancer patients. VTE is the second most common cause of death among patients with cancer, and cancer-associated VTE is be-coming increasingly prevalent. Therefore, early diagnosis and treatment of cancer-associated VTE is particularly important. This study presents a pancreatic cancer-associated deep vein thrombosis (DVT) patient who engaged in a multidisciplinary comprehensive discus-sion in the Interventional Therapy Department, Tianjin Medical University Cancer Hospital to enhance concern, interdisciplinary com-munication, and cooperation in terms of cancer-associated VTE diagnosis and treatment strategies.