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OBJECTIVE: PARP inhibitors combined with antiangiogenic drugs have been reported to improve outcomes in BRCA wild-type ovarian cancer patients, the mechanism of the combination is unclear. In this study, we explored the mechanism of apatinib combined with olaparib in the treatment of ovarian cancer. METHODS: In this study, human ovarian cancer cell lines A2780 and OVCAR3 were used as experimental objects, and the expression of ferroptosis-related protein GPX4 after treatment with apatinib and olaparib was detected by Western blot. The SuperPred database was used to predict the target of the combined action of apatinib and olaparib, and the predicted results were verified by Western blot experiment to explore the mechanism of ferroptosis induced by apatinib and olaparib. RESULTS: Apatinib combined with olaparib-induced ferroptosis in p53 wild-type cells, and p53 mutant cells developed drug resistance. The p53 activator RITA sensitized drug-resistant cells to ferroptosis induced by apatinib combined with olaparib. Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. CONCLUSION: This discovery revealed the specific mechanism of ferroptosis induced by apatinib combined with olaparib in p53 wild-type ovarian cancer cells and provided a theoretical basis for the clinical combined use of apatinib and olaparib in p53 wild-type ovarian cancer patients.

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Objective:To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO).Method:The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH 4 (methane) and H 2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman′s Rank correlation analysis,and the Z test were used for statistical analysis. Results:Based on the international recommended diagnostic criteria for SIBO,which are fasting CH 4 ≥10 ppm (parts per million) or H 2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH 4 and H 2 were higher in the case group than in the control group [CH 4: 3(2,7) vs. 3(1,3) ppm, H 2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH 4 levels was statistically significant ( Z=6.22, P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH 4 alone,0.531 for H 2 alone, and 0.620 for CH 4 combined with H 2. The cut-off values were fasting CH 4≥4 ppm,fasting H 2≥13 ppm,and fasting CH 4 ≥5 ppm (or CH 4≥4 ppm and H 2≥24 ppm),respectively. Measuring CH 4 alone and CH 4 combined with H 2 was effective for determining the presence of gastrointestinal symptoms ( P<0.05). When CH 4 alone or CH 4 combined with H 2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria ( P>0.05). The specificity of CH 4 alone was 79.9%,and the accuracy of CH 4 alone was 68.8%. The specificity of CH 4 combined with H 2 was 85.0%,and the accuracy of CH 4 combined with H 2 was 71.7%. Conclusion:Rapid one-time determination of CH 4 and H 2 in exhaled breath may a viable diagnostic method for SIBO, and using CH 4 combined with H 2 ( i.e.,fasting CH 4≥5 ppm, or CH 4 ≥4 ppm and H 2 ≥24 ppm) as cutoff values may be feasible.

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Objective:To analyze the current situation of the specialty setting and training program of Intelligent Medical Engineering (IME) in China.Methods:The information about the schools' name, year of opening, enrollment plan, training objective and curriculum was obtained by the website investigation and was statistically analyzed by Excel.Results:(1)A total of 48 universities set an IME major from 2018 to 2021, mainly in developed areas. The number of talent training was nearly 2 400 per year. (2)The information of colleges which established IME was acquired from 47 universities. Among them, 59% (13/22) of the comprehensive universities set the IME major in medical-related colleges. (3)The information concerning professional training objectives was collected from 40 universities and they highlighted the capabilities of big data intelligent processing and software research and development, and 12 of them also required students to master the capability of hardware research and development. (4)Computer science and technology, preclinical medicine, clinical medicine and biomedical engineering were the main disciplines of IME. The professional core curriculum mainly included computer language and artificial intelligence (AI) related courses.Conclusion:IME education has sprung up rapidly with the development of AI technology in medical and health field. However, the cultivation of IME professionals is still at exploratory stage. It is recommended that the national related departments should publish some relevant guidelines on the training orientation of IME.

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BACKGROUND: The aim was to assess the clinical Glasgow-Blatchford score (GBS), Rockall score (CRS), and AIMS65 score in predicting outcomes (rebleeding, need for intervention, and length of stay) among patients with small bowel hemorrhage. METHODS: We conducted a retrospective study of patients with small bowel bleeding (SBB). Rebleeding, need for intervention, and length of stay was investigated by 3 scoring systems. The area under the receiver operator characteristic curve was used to analyze the performance of 3 scoring systems. RESULTS: Among 162 included patients, the scores of rebleeding, intervention, and length of stay ≥10 days groups were higher than no rebleeding, non-intervention, and length of stay <10 days groups, respectively (P < .05). The CRS, GBS, and AIMS65 scoring systems demonstrated statistically significant difference in predicting rebleeding (AUROC 0.693 vs. 0.790 vs. 0.740; all P < .01), intervention (AUROC: 0.726 vs. 0.825 vs. 0.773; all P < .01) and length of stay (AUROC 0.651 vs. 0.631 vs. 0.635; all P < .05). Higher cut-off scores achieved better sensitivity/specificity [rebleeding (CRS > 2, GBS > 7, AIMS65 > 0); need for intervention (CRS > 2, GBS > 7, AIMS65 > 0); length of stay (CRS > 0, GBS > 7, AIMS65 > 1)] in the risk stratification. CONCLUSIONS: The GBS system is reliable to be recommended for routine use in predicting rebleeding and the need for intervention for early decision making in patients with SBB. The 3 scoring systems are poorly useful in predicting length of stay.

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Reducing radiation dose in cardiac catheter-based X-ray procedures increases safety but also image noise and artifacts. Excessive noise and artifacts can compromise vital image information, which can affect clinical decision-making. Developing more effective X-ray denoising methodologies will be beneficial to both patients and healthcare professionals by allowing imaging at lower radiation dose without compromising image information. This paper proposes a framework based on a convolutional neural network (CNN), namely Ultra-Dense Denoising Network (UDDN), for low-dose X-ray image denoising. To promote feature extraction, we designed a novel residual block which establishes a solid correlation among multiple-path neural units via abundant cross connections in its representation enhancement section. Experiments on synthetic additive noise X-ray data show that the UDDN achieves statistically significant higher peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) than other comparative methods. We enhanced the clinical adaptability of our framework by training using normally-distributed noise and tested on clinical data taken from procedures at St. Thomas' hospital in London. The performance was assessed by using local SNR and by clinical voting using ten cardiologists. The results show that the UDDN outperforms the other comparative methods and is a promising solution to this challenging but clinically impactful task.

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BACKGROUND@#AND PURPOSE: Previous studies have explored the association between retinal vascular changes and cognitive impairment. The retinal vasculature shares some characteristics with the cerebral vasculature, and quantitative changes in it could indicate cognitive impairment. Hence, a comprehensive meta-analysis was performed to clarify the potential relationship between retinal vascular geometric changes and cognitive impairment.@*METHODS@#Relevant databases were scrupulously and systematically searched for retinal vascular geometric changes including caliber, tortuosity, and fractal dimension (FD), and for cognitive impairment. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of included studies. RevMan was used to perform the meta-analysis and detect publication bias. Sensitivity analyses were also performed.@*RESULTS@#Five studies that involved 2,343 subjects were finally included in the meta-analysis. The results showed that there was no significant association between central retinal artery equivalents (Z=1.17) or central retinal venular equivalents (Z=1.74) and cognitive impairment (both p>0.05). Similarly, no significant difference was detected in retinal arteriolar tortuosity (Z=0.91) and venular tortuosity (Z=1.31) (both p>0.05). However, the retinal arteriolar FD (mean difference: −0.03, 95% CI: −0.05, −0.01) and venular FD (mean difference: −0.03, 95% CI: −0.05, −0.02) were associated with cognitive impairment.@*CONCLUSIONS@#A smaller retinal microvascular FD might be associated with cognitive impairment. Further large-sample and well-controlled original studies are required to confirm the present findings.

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Objective:To compare the risk assessment capability of model for end-stage liver disease (MELD), glasgow-blatchford score (GBS), and the AIMS65 scoring system for liver cirrhosis patients with esophageal and gastric variceal bleeding (EGVB).Methods:A retrospective analysis was made on data of 182 cirrhosis patients with EGVB admitted to the Department of Gastroenterology, General Hospital of Tianjin Medical University from January 1, 2015 to March 1, 2018. According to the MELD, GBS and AIMS65 scoring system, the corresponding scores of each patient were calculated to evaluate the ability of the three scoring systems to correctly classify EGVB as a " high-risk patient" . The receiver operating characteristic curve was drawn to compare the predictive value of three scoring systems for different clinical outcomes (blood transfusion, rebleeding, and death). The area under curve (AUC)>0.7 was believed to have higher accuracy.Results:The clinical outcomes of 182 patients included blood transfusion in 113 (62.1%) cases, rebleeding in 31 (17.0%) cases, and death of 11 (6.0%) cases. The MELD score was 7-25, GBS was 3-16, and AIMS65 score was 0-3. There were 4 (2.2%) patients with MELD score < 9, 139 (76.4%) patients with AIMS65 score 0-1, including 68 patients with AIMS65 score of 0 and 71 patients with AIMS65 score of 1. The AUC of MELD, GBS and AIMS65 for predicting blood transfusion was 0.514 (95% CI: 0.439-0.589), 0.681 (95% CI: 0.608-0.748), and 0.669 (95% CI: 0.596-0.737), respectively. When predicting rebleeding, the AUC of MELD, GBS and AIMS65 was 0.525 (95% CI: 0.449-0.599), 0.528 (95% CI: 0.453-0.602) and 0.580 (95% CI: 0.505-0.652), respectively. When predicting in-hospital mortality, the AUC of MELD, GBS and AIMS65 was 0.642 (95% CI: 0.567-0.711), 0.581 (95% CI: 0.505-0.653) and 0.786 (95% CI: 0.719-0.843), respectively. AIMS65 was superior to MELD ( P=0.083 6) and GBS ( P=0.047 0). Conclusion:GBS can correctly classify cirrhosis patients with EGVB as " high-risk group" , and is better than AIMS65 and MELD scoring system. MELD, GBS and AIMS65 all have poor accuracy in predicting blood transfusion and rebleeding, AIMS65 has a higher predictive value for death.

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Objective@#To investigate the prognostic value of albumin-to-bilirubin scores in the assessment of autoimmune hepatitis-related cirrhosis.@*Methods@#The receiver operating characteristic curve was used to evaluate the accuracy of ALBI, Child-Pugh and model for end-stage liver disease (MELD) for prognosis prediction. Survival analysis was performed according to the ALBI classification. Spearman correlation analysis was performed on the ALBI score and the Child-Pugh score. Survival curves were plotted by Kaplan-Meier method, and Log-rank method was used to compare the survival difference curves between different groups.@*Results@#149 patients were recruited in the study. The ROC analysis showed that the ALBI scores (0.861, 0.826, 0.779, 0.744)was superior to Child-Pugh scores(0.703, P = 0.006; 0.672, P < 0.001; 0.613, P < 0.001; 0.583, P < 0.001)and MELD score(0.774, P = 0.031; 0.731, P = 0.007; 0.669, P < 0.001; 0.631, P < 0.001) for predicting 6, 12, 24, and 36 months mortality. Patients with ALBI grade 3 had a significantly lower survival rate than those with ALBI grade1 and grade 2.@*Conclusion@#ALBI score may be useful to evaluate the long-term prognosis of patients with autoimmune hepatitis-related cirrhosis.

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Objective To investigate and analyze the applications of liver grafts from donation after death children (≤5 kg) in pediatric liver transplantation.Methods A retrospective analysis was conducted on 18 cases of pediatric recipients using liver grafts from donation after death children (≤5 kg) during January 2013 to December 2015.The survival rate of patients,recovery of liver function,incidence of lung infection,vascular complications and biliary complications were observed,and the causes of deaths were analyzed.Results The median follow-up time of all the patients was 28.4 months (0.06-52.2 months).The 1-and 3-year cumulative survival rate was the same 88.9％,the incidence of lung infection was 22.2％,of vessel complications was 33.3％,and biliary complication rate was 11.1％.Two cases died after liver transplantation.Conclusion The applications of liver donation after death children (≤5 kg) were satisfactory,but there is still relatively limited experience,and further observation and research are needed.

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OBJECTIVE: To obtain the microcrystal agents of sorafenib and examine the in vivo anti-tumor efficiency of sorafenib-microcrystal on hepatocellular carcinoma cells. METHODS: The solubilizing solution or microcrystal of sorafenib was obtained. A highly aggressive HCC cell line, MHCC97-H, was used to form the subcutaneous or intra-hepatic tumor model in nude mice. Sorafenib-solution or microcrystal was injected into tumors. The clearance curve or anti-tumor efficiency of solubilizing solution or microcrystal was identified. Endogenous of EMT related indicators was identified by qPCR. RESULTS: Sorafenib slowly released in tumor tissues by sorafenib-microcrystal but not sorafenib-solution. Treatment of sorafenib-microcrystal inhibited the in vivo growth of MHCC97-H cells. CONCLUSION: The microcrystal agents of sorafenib is prepared. This work also establishes the in vivo anti-tumor efficiency of sorafenib-microcrystal on HCC cells.

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Objective To investigate the diagnostic value of endoscopic ultrasonography(EUS)for esophageal submucosal tumor(SMT). Methods Clinical data of 388 patients with esophageal SMT, who underwent EUS and endoscopic treatment in Tianjin Medical University General Hospital were collected from May 2010 to September 2016. The golden standard for the origin of esophageal SMT was the diagnosis during endoscopic treatment, and the golden standard of pathological type was the combination of postoperative pathological and immunohistochemical findings. The diagnostic accuracy of EUS for esophageal SMT was evaluated. Results The conventional endoscopy revealed that 31.70%(123/388)and 43.81%(170/388)esophageal SMTs were located in the middle and lower segments of esophagus,respectively. The diagnostic consistency of EUS for the origin of lesion was 71.51%(251/351), while the diagnostic consistency of EUS for lesion originated from the muscularis mucosae, submucosa and muscularis propria layer was 92.90%(170/183), 34.38%(11/32), and 51.47%(70/136), respectively. The diagnostic consistency of EUS for the type of lesion was 81.00%(260/321), while the diagnostic consistency of leiomyoma, esophageal cyst, and lipoma were 88.42%(252/285), 14.81%(4/27), and 80.00%(4/5), respectively. Conclusion EUS can preliminarily diagnose the origin and pathological type of esophageal SMT,but there are limitations on the diagnosis of uncommon lesions,which need combination of pathological and immunohistochemical findings.

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Objective To evaluate the predictive value of Admission-Rockall Score (aRS), Full-Rockall Score ( fRS ), Glasgow-Blatchford Score ( GBS ) and AIMS65 scoring systems for rebleeding, mortality, transfusion and clinical intervention of patients with acute nonvariceal upper gastrointestinal bleeding ( ANVUGIB). Methods A retrospective study was performed on the data of 294 ANVUGIB inpatients in the Department of Gastroenterology of Tianjin Medical University General Hospital from January 2015 to September 2016. Each patient was graded using the four scoring systems. The area under the receiver-operating characteristic curve ( AUC) about rebleeding, mortality, blood transfusion and clinical intervention was calculated using each system. Results For predicting rebleeding, fRS (AUC＝0. 696) and GBS (AUC＝0. 697) were both superior to aRS (AUC＝0. 609, P＜0. 05) and AIMS65 (AUC＝0. 571, P＜0. 05), and there was no significant difference on AUC between fRS and GBS (P＞0. 05). For predicting mortality, the AUC of aRS, fRS, GBS and AIMS65 were 0. 755, 0. 791, 0. 818, and 0. 780, respectively, and there were no significant differences (P＞0. 05). There were no significant differences in the predicting transfusion among four scoring systems, and the AUC was 0. 625, 0. 626, 0. 697 and 0. 658, respectively. Regarding clinical intervention treatment, fRS (AUC＝0. 661) was superior than that of aRS (AUC＝0. 520, P＜0. 05) and AIMS65 (AUC＝0. 545, P＜0. 05), and the AUC of GBS and three other scoring systems had no significant differences (P＞0. 05). Conclusion The four scoring systems are all with good predicting value on mortality of patients with ANVUGIB, while not on other aspects including rebleeding, transfusion and clinical intervention. fRS has a slightly better value on prediction of rebleeding and clinical intervention, and GBS is slightly better on prediction of rebleeding.

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Objective To more effectively prevent hypertension and provide better health care for college and university teachers and staff by keeping abreast with the epidemiology of hypertension. Methods The data were extracted from the selected Chinese and English papers on epidemiology of hypertension, which was followed by a meta-analysis of the prevalence, awareness rate, cure rate, and control rate of hypertension in college and university teachers and staff of China. Results A total of 73 papers were included in this study. The total prevalence of hypertension was 23. 3% (95%CI=21. 1%-25. 6%), the prevalence of hypertension was 27. 2% (95%CI=24. 4%-30. 0%) in male hypertensive teachers and staff and was 18. 6% (95%CI=16. 6%-20. 6%) in female hypertensive teachers and staff. The prevalence of hypertension increased with the increasing age and tended to increase with the year of investigation in college and university teachers and staff of China, and was the lowest in East China followed by Central China and West China. The awareness rate, cure rate and control rate of hypertension were 68. 3% (95%CI=59 . 7%-76 . 8%) , 63 . 7% ( 95%CI=55 . 5%-71 . 9%) , and 37 . 7% ( 95%CI=28 . 0%-47 . 5%) respec-tively in college and university teachers and staff of China. Conclusion The prevalence of hypertension is different in college and university teachers and staff of China due to different sexes, ages and areas.

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Objective To more effectively prevent hypertension and provide better health care for college and university teachers and staff by keeping abreast with the epidemiology of hypertension. Methods The data were extracted from the selected Chinese and English papers on epidemiology of hypertension, which was followed by a meta-analysis of the prevalence, awareness rate, cure rate, and control rate of hypertension in college and university teachers and staff of China. Results A total of 73 papers were included in this study. The total prevalence of hypertension was 23. 3% (95%CI=21. 1%-25. 6%), the prevalence of hypertension was 27. 2% (95%CI=24. 4%-30. 0%) in male hypertensive teachers and staff and was 18. 6% (95%CI=16. 6%-20. 6%) in female hypertensive teachers and staff. The prevalence of hypertension increased with the increasing age and tended to increase with the year of investigation in college and university teachers and staff of China, and was the lowest in East China followed by Central China and West China. The awareness rate, cure rate and control rate of hypertension were 68. 3% (95%CI=59 . 7%-76 . 8%) , 63 . 7% ( 95%CI=55 . 5%-71 . 9%) , and 37 . 7% ( 95%CI=28 . 0%-47 . 5%) respec-tively in college and university teachers and staff of China. Conclusion The prevalence of hypertension is different in college and university teachers and staff of China due to different sexes, ages and areas.

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Objective To investigate the clinical features,therapeutic methods,therapeutic effect and prognosis of a case of bladder urothelial carcinoma patients in combination with trophoblast.Methods The pathological data of a patient with bladder high grade urinary epithelial carcinoma in combination with trophoblast was retrospectively analyzed and the related literatures were reviewed.It was a male patient,69 years old,presenting with total painless gross hematuria.The CT scan showed irregular nodules on the anterior wall of bladder.Results Cystoscopy showed 1.5 cm cauliflower mass on the anterior wall of bladder,and transurethral resection of bladder tumor was performed.The pathology and immunohistochemistry showed urothelial carcinoma.Lung metastases was found due to hemoptysis,and increased serum beta human chorionic gonadotropin (β-HCG) was detected simuhaneously.Pathology was double checked and bladder urothelial carcinoma with trophoblast cell differentiation was considered.Three cycles gemcitabine + cisplatin (GC regimen) and 2 cycles etoposide + methotrexate + vincristine + cyclophosphamide (modified EMA-CO regimen) therapies were given,and the disease was stable at that time.The patient died on June 10,2016,and the total survival period was 9 months.Conclusions The clinical and imaging of urothelial carcinoma with trophoblast differentiation is not special.Diagnosis must depend on the pathological and immunohistochemistry examinations.The efficacy can be evaluated by combining imaging with serumβ-HCG.Treatment should be systemic venous chemotherapy.

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The unbalanced allocation and sharing of medical and health information resources have retrained the medical and health information construction in China. The current allocation of medical and health information re-sources was thus summarized in this paper by analyzing the CNKI. net-covered literature on medical and health in-formation, the number of undergraduates in colleges and universities, the number of employed medical and health information professionals in Eastern, Central and Western China, and in different provinces of China using the RSR, and suggestions were put forward for the development of medical and health cause in our country.

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Objective To retrospectively analyze the status quo of health education for domestic hypertensive patients in the past 10 years.Methods Papers on health education for domestic hypertensive patients, retrieved from Wanfang Database and CNKI, were analyzed according to the Excel.Results The number of studies on health education for domestic hypertensive patients showed a tendency to increase in 2005-2015.The commonly used health education methods for hypertensive patients were face to face education, distributing education materials, holding lectures, and follow-up.The main health education contents included hypertension-related knowledge, physical exercises, rational diet, emotion control, compliant behaviors, giving up smoking and limiting drinking, and body weight control.The index of lifestyle of patients was improved after health education.Conclusion Great achievements are made in health education for hypertensive patients in our country.Stress should be placed on the rational planning for health education and building electronic health education platform in future.

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Using the concept and method of evidence-based medicine,the paper systematically analyzes the functions and shortage of intelligent health Application (App) in disease diagnosis,treatment and self-management,and describes the functions of health and disease management App,so as to promote the development of App and enable App to better assist in health management.

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The paper discusses the evidence-based decision-making framework for medical insurance reimbursement based on big data concept through expert consultation,defines the dimension of decision-making,analyzes the evidence-based decision-making steps in combination with big data resources,proposes suggestions on how to make full use of big data resources around medical insurance decision-making practice.

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Based on the introduction to the clinical phenotype extraction technique,the paper conducts systematic review on the extraction of clinical phenotype from Electronic Medical Records (EMR) of diabetes by taking advantages of the clinical decision support technique,natural language processing technique and machine learning method,and indicates that the deep learning method can be used to extract clinical phenotype from the EMR data more effectively and accurately,help clinical researchers better conduct clinical tests,and improve the medical care level.