Objective:To investigate the value of CT quantitative parameters of tumor and spleen in predicting the clinical stage of gastric cancer (Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage).Methods:This study was a case-control study. The data of 145 patients with gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from February 2019 to June 2021 were retrospectively collected, including 70 cases of Ⅰ/Ⅱ stage and 75 cases of Ⅲ/Ⅳ stage. On the baseline CT images, the tumor related parameters, including tumor thickness, length of tumor, CT attenuation of tumor unenhanced phase, CT attenuation of tumor arterial phase, CT attenuation of tumor venous phase were measured. The spleen related parameters, including splenic thickness, CT attenuation of splenic unenhanced phase, CT attenuation of splenic arterial phase, CT attenuation of splenic venous phase, and standard deviation of CT attenuation (CTsd) in splenic unenhanced phase were also measured. The independent sample t test or Mann-Whitney U test was used to compare the parameters between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage patients. The multi-factor logistic regression analysis was used to find the independent predictors of gastric cancer clinical stage, and establish the combined parameters. The efficiency to the diagnosis of gastric cancer stage of single and combined parameters was evaluated using the operating characteristic curve, and the DeLong test was used to compare the differences of area under the curve (AUC). Results:There were significant differences in tumor thickness, length of tumor, CT attenuation of tumor venous phase, CT attenuation of splenic unenhanced phase, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage of gastric cancer ( P<0.05). Multivariate analysis showed that tumor thickness ( OR=1.073, 95% CI 1.026-1.123, P=0.002), CT attenuation of splenic venous phase ( OR=1.040, 95% CI 1.011-1.070, P=0.006) and CTsd in splenic unenhanced phase ( OR=1.625, 95% CI 1.330-1.987, P<0.001) were independent risk factors for the clinical stage of gastric cancer and the combined parameters were established. The AUC values of tumor thickness, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase and combined parameters were 0.655, 0.614, 0.749 and 0.806, respectively. The AUC of combined parameters was higher than those of tumor thickness and CT attenuation of splenic venous phase, and the differences were statistically significant ( Z=3.37, 3.82, both P<0.001). Conclusion:Tumor thickness, CT attenuation of splenic venous phase and CTsd in splenic unenhanced phase are independent risk factors for the clinical stage of gastric cancer, and combined parameters can improve the diagnostic efficiency.

Objective To analyze the mortality characteristics and trends and the cause-eliminated life expectancy of gastric cancer in Harbin City from 1987 to 2019. Methods Mortality data of residents with gastric cancer from 1987 to 2019 in Harbin was analyzed to describe the mortality characteristics and trends of gastric cancer. Abridged life table and cause-eliminated life table were applied to calculate life expectancy and cause-eliminated life expectancy. Average annual percentage change (AAPC) was calculated with Joinpoint 4.2 software to evaluate the trends of mortality and cause-eliminated life expectancy of gastric cancer. Results From 1987 to 2019, the crude mortality, ASMRC and ASMRW and the truncated rate (35-64) were 14.3/10⁵, 10.9/10⁵, 10.9/10⁵, and 13.5/10⁵, respectively. The ASMRC showed an obvious decreasing trend at an average annual rate of 2.9% from 1987 to 2019 (95%CI: -4.4%--1.4%). Significant decreasing trends were observed for males (AAPC=-3.0%, 95%CI: -4.4%--1.7%) and females (AAPC=-3.1%, 95%CI: -5.3%--0.9%). An obvious decreasing trend in the ASMRW was also observed. The truncated rate (35-64) showed a downward trend (AAPC=-2.8%, 95%CI: -3.1%--2.5%). The average life expectancy of residents from 1987 to 2019 in Harbin were 76.78 years (male: 74.41 years, female: 79.33 years). After eliminating the causes of death of gastric cancer, the life expectancy increased by 0.25 years (male: 0.31 years, female: 0.18 years). Significant decreasing trends were found in the proportion of gastric cancer in all malignant cancer cases (AAPC=-0.18%, 95%CI: -2.0%--1.7%). Conclusion The mortality of gastric cancer decreases gradually from 1987 to 2019 in Harbin. After eliminating the causes of death of gastric cancer, the life expectancy increases by 0.25 years. Therefore, prevention and control should be strengthened.

Objective:To evaluate the value of preoperative prediction of vessel invasion (VI) of locally advanced gastric cancer by machine learning model based on the venous phase enhanced CT radiomics features.Methods:A retrospective analysis of 296 patients with locally advanced gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from July 2011 to December 2020 was performed. The patients were divided into VI positive group ( n=213) and VI negative group ( n=83) based on pathological results. The data were divided into training set ( n=207) and test set ( n=89) according to the ratio of 7∶3 with stratification sampling. The clinical characteristics of patients were recorded, and the independent risk factors of gastric cancer VI were screened by multivariate logistic regression. Pyradiomics software was used to extract radiomic features from the venous phase enhanced CT images, and the minimum absolute shrinkage and selection algorithm (LASSO) was used to screen the features, obtain the optimal feature subset, and establish the radiomics signature. Four machine learning algorithms, including extreme gradient boosting (XGBoost), logistic, naive Bayes (GNB), and support vector machine (SVM) models, were used to build prediction models for the radiomics signature and the screened clinical independent risk factors. The efficacy of the model in predicting gastric cancer VI was evaluated by the receiver operating characteristic curve. Results:The degree of differentiation (OR=13.651, 95%CI 7.265-25.650, P=0.003), Lauren′s classification (OR=1.349, 95%CI 1.011-1.799, P=0.042) and CA199 (OR=1.796, 95%CI 1.406-2.186, P=0.044) were independent risk factors for predicting the VI of locally advanced gastric cancer. Based on the venous phase enhanced CT images, 864 quantitative features were extracted, and 18 best constructed radiomics signature were selected by LASSO. In the training set, the area under the curve (AUC) of XGBoost, logistic, GNB and SVM models for predicting gastric cancer VI were 0.914 (95%CI 0.875-0.953), 0.897 (95%CI 0.853-0.940), 0.880 (95%CI 0.832-0.928) and 0.814 (95%CI 0.755-0.873), respectively, and in the test set were 0.870 (95%CI 0.769-0.971), 0.877 (95%CI 0.788-0.964), 0.859 (95%CI 0.755-0.961) and 0.773 (95%CI 0.647-0.898). The logistic model had the largest AUC in the test set. Conclusions:The machine learning model based on the venous phase enhanced CT radiomics features has high efficacy in predicting the VI of locally advanced gastric cancer before the operation, and the logistic model demonstrates the best diagnostic efficacy.

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

OBJECTIVE: Sort out and analyze the current status and existing problems of the pilot work of the medical device marketing authorization holder system to provide reference opinions for the full implementation of the medical device marketing authorization holder system. METHODS: Use literature analysis, comparative analysis and field research to comprehensively analyze the status, advantages and risks of commissioned production under the medical device marketing authorization holder system. RESULTS: The commissioned production under the medical device marketing authorization holder system brings dividends and also brings risks. CONCLUSIONS We should consider improving the medical device marketing authorization holder system from marketing authorization holder, the entrusted manufacturer, and the regulatory authority, and strengthen the quality supervision of the entrusted production of products.
China ; Marketing

Objective:To investigate the changes of brain energy metabolism and cognitive function in mice with specifically knocking out AMP-activated protein kinase α1 subunit ( AMPKα1) gene in the excitatory neurons by Cre-loxP recombination system. Methods:Sixteen 6-month-old mice with genotype AMPKα1 flox/flox/Camk2a-Cre/ERT2 obtained by hybrid breeding were randomly divided into AMPKα1 knockout group ( n=8) and AMPKα1 wild-type group ( n=8). Mice in the AMPKα1 knockout group were intraperitoneally injected 0.1 mL tamoxifen (20 mg/mL, dissolved in corn oil) daily for a consecutive 5 d to control AMPKα1 gene knockout in the excitatory neurons; and mice in the AMPKα1 wild-type group were intraperitoneally injected 0.1 mL corn oil daily for a consecutive 5 d. Seven d after that, Morris water maze and T maze experiments were employed to detect the spatial learning and memory abilities and spatial working memory of these mice; chemical exchange saturation transfer imaging (CEST) was used to observe the glucose metabolism in the hippocampus and cortex surrounding the hippocampus; Western blotting was used to detect the AMPKα1 and glutamate receptor 1 (GluR1) protein expressions in the hippocampus and cortex surrounding hippocampus of two groups. Results:(1) Morris water maze showed that, as compared with those in the AMPKα1 wild-type group, mice in the AMPKα1 knockout group had significantly prolonged escape latency ([13.90±3.72] s vs. [22.40±6.28] s; [11.95±3.86] s vs. [22.39±9.77] s]) on the 3 rd and 4 th d of experiment, statistically decreased times crossing the platform ([5.25±1.83] times vs. [1.75±1.28] times, P<0.05). (2) T-maze experiment showed that as compared with that of the AMPKα1 wild-type group, the free alternation rate in mice of the AMPKα1 knockout group was significantly decreased ([73.21±9.16]% vs. [48.21±11.29]%, P<0.05). (3) CEST showed that the glucose metabolism levels in the hippocampus and cortex surrounding the hippocampus of AMPKα1 knockout group were significantly lower than those in AMPKα1 wild-type group (1.51±0.81 vs. 2.77±0.67; 1.31±0.83 vs. 2.42±0.95, P<0.05). (4) Western blotting showed that the AMPKα1 and GluR1 protein expressions in the hippocampus and cortex surrounding the hippocampus of the AMPKα1 wild-type group were significantly higher than those of the AMPKα1 knockout group (AMPKα1: 0.70±0.05 vs. 0.49±0.03, 0.98±0.04 vs. 0.64±0.06; GluR1: 1.22±0.18 vs. 0.60±0.11, 0.96±0.08 vs. 0.79±0.04, P<0.05). Conclusion:Specifically knocking out AMPKα1 in excitatory neurons can result in abnormal glucose metabolism in the brain of mice, and thus cause cognitive dysfunction, whose mechanism may be related to excitatory synaptic disorder caused by energy metabolism disorder.

Tumor is a complex systemic disease, involving abnormalities at multiple levels, such as DNA, RNA, protein and metabolite. According to the central rule, the derived omics methods are genomics, transcriptomics, proteomics and metabonomics. In the past few decades, there have been remarkable achievements in the single omics study of tumor, but the exact mechanism of tumor development is still unclear. In order to reveal the process of tumorigenesis and development in a more systematic way, the research of multiomics came into being, which promoted the transformation of tumor research paradigm from single parameter model to multi parameter system model. The integration of multi-omics methods is expected to clarify the mechanism of tumor occurrence and development, find biomarkers with diagnostic, prognostic and predictive performance, explore new treatment targets, and finally achieve predictive, preventive, and personalized medicine (PPPM). This paper reviews the research methods and progress of different omics techniques in tumor research, especially emphasizes the importance and scientific value of the integration of multiple omics techniques in tumor research and clinical related results.

Objective: To assess the incidence and related risk factors of postoperative intraabdominal infection in patients undergoing anatomical hepatectomy. Methods: The clinical data from 122 patients who underwent anatomical major hepatectomy in our institution were retrospectively analyzed. The electronic medical data were retrieved for further analysis including the amount of crystalloid and colloid fluid infused, intraoperative estimated blood loss, volume of blood transfusion, the dosage of vasoactive drugs, postoperative liver function, inflammation index, the incidence of intraabdominal infection and the length of hospital stay (LOS). Results: Patients were divided into infection group (n=39) and non- infection group (n=83). Intraabdominal infection was correlated with preoperative cirrhosis, the elevated direct bilirubin and alanine aminotransferase, the duration of operation, bilioenteric anastomosis or cholangiotomy, the infusion volume of colloid and crystalloid fluid, transfusion volume, direct bilirubin level on the POD 1(post-operation on day 1) (P<0.05); Multivariate analysis showed the incidence of intraabdominal infection was highly correlated with the amount of intraoperative colloid fluid bilioenteric anastomosis(P<0.05). Conclusions Intraoperative infused volume of synthetic colloid, along with bilioenteric anastomosis are independent risk factors for postoperative intraabdominal infection.

Objective To explore the effect of electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on motor behaviors, the axonal integrity and nerve bundle of motor cortex and striatum in rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) using diffusion tensor imaging (DTI). Methods Thirty-six adult male Sprague-Dawley rats were randomly assigned to sham opera-tion group (sham group), ischemia control group (model group) and electroacupuncture treatment group (EA group) with twelve rats in each group. The later two groups were occluded their middle cerebral arteries for two hours. Twenty-four hours after modeling, EA group re-ceived electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on the paralyzed limb, once a day, for 14 days. They were assessed with modified Neurological Severity Scores (mNSS) and Rota-rod test, and scanned with small animal magnetic resonance imaging system for T2-weighted image (T2WI) and DTI, the infarct size, related fractional anisotropy (rFA) and related number of tracks of motor cortex and striatum were recorded. Results Compared with the sham group, the score of mNSS increased in the model group and EA group after model-ing, and was lower in EA group than in the model group seven days and 14 days after intervention (P<0.05). Rota-rod test showed that the retention time was significantly longer in EA group than in the model group (P<0.05). T2WI showed that the infarct size was smaller in EA group than in the model group (P<0.05). DTI showed that rFA in motor cortex and striatum was higher in EA group than in the model group (P<0.05), as well as the related number of tracks (P<0.05) in motor cortex. Conclusion Electroacupuncture at Quchi and Zusanli acupoints could improve the motor function in rats with ischemic stroke, which may be related to the recovery of nerve bundle of motor cortex and stri-atum in ischemic side.

Objective To investigate the relationship between learning and memory deficit and demyelination of the corpus callosum in twelve-month old APP/PS1 transgenic mice. Methods Twelve twelve-month old APP/PS1 transgenic mice were as AD group, and age-matched wild type (WT) littermates were as WT group. Learning and memory ability was tested with Morris water maze, and the mor-phology of nerve fiber of corpus callosum was detected with Luxol Fast Blue staining. Immunohistochemistry was used to detect myelin ba-sic protein (MBP) in the corpus callosum. Thioflavine S staining was used to detect amyloid plaque in the corpus callosum. Results Com-pared with WT group, the latency increased (Z>2.873, P<0.01) and the times crossing the location of the platform decreased (t=-7.339, P<0.001) in AD group. The nerve fibers were sparse and disorganized, with a lot of vacuoles in the corpus callosum of AD group. The positive expression of MBP in the corpus callosum was significantly decreased (t=-4.481, P<0.001) in AD group compared with WT group. There were amyloid plaques in the corpus callosum of AD group. Conclusion Twelve-month old APP/PS1 transgenic mice exhibit learning and memory deficit, which may be attributed to the deposition of the amyloid plaque mediated demyelinated injury of the corpus callosum.