Objective:The aim is to construct an evaluation framework for clinical research benefits,and provide a reference for the formulate of evaluation standards for clinical research benefits.Methods:The Delphi method was used to carry out expert consultation,and the mean,score of importance,coefficient of variation and coordination,etc.of evaluation indicators were summarized and calculated,to screen evaluation indicators for clinical research benefits.Results:Twenty-three experts in this field were selected for correspondence,and their enthusiasm was 100%in both rounds,the authority coefficients were≥0.90,and Kendall's coefficients of concordance were<0.25(P<0.001).By referring to the mean and coefficient of variation of the indicators,as well as combining them with expert suggestions,an evaluation framework for clinical research benefits was ultimately formed with 2 primary indicators,5 secondary indicators,and 8 tertiary indicators.Conclusion:The evaluation framework for clinical research benefits constructed in this paper can comprehensively evaluate the research benefits,as well as provide a basis for reasonably determining the research risk-benefit ratio and developing quantitative evaluation tools for clinical research benefits.

Objective To survey the levels and distributed status of serum vitamin D in children in Hanzhong city of Shaanxi,and provide a basis for the prevention of children with vitamin D deficiency.Methods A total of 6 780 children aged 1 to 6 years from March 2019 to February 2021 in Children's Health Clinic of Hanzhong Center Hospital for physical examination were selected as subjects.The levels of serum 25-hydroxyvitamin D[25(OH)D],serum 25-hydroxyvitamin D2[25(OH)D2]and serum 25-hydroxyvitamin D3[25(OH)D3]were measured by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the factors of ages and sexes and seasons were analyzed.Results The levels of serum 25(OH)D,25(OH)D2 and 25(OH)D3 in all children were 38.24±9.84 ng/ml,2.31±3.91 ng/ml and 35.93±9.93 ng/ml,respectively.The vitamin D deficiency rate,insufficiency rate and adequacy rate were 2.75％(186/6 780),18.29％(1 240/6 780)and 78.96％(5 354/6 780),respectively.The levels of serum 25(OH)D and 25(OH)D3 in children aged 1～2,2～3 and 3～6 years were gradually decreased with the growth of age,while the rate of vitamin D deficiency was increased,with significant differences(F=1 153.499,1 165.341,1 374.051,all P＜0.05).There were no significant differences in distributed status of serum of vitamin D and the levels of serum 25(OH)D,25(OH)D2 and 25(OH)D3 levels among different genders(t/x2=0.727,1.271,0.222,2.659,all P＞0.05).The levels of serum 25(OH)D and 25(OH)D3 in winter were lower than those in spring,summer and autumn,and the differences were statistically significant(q=6.853,7.281,6.801;5.341,6.225,5.989,all P＜0.01).The vitamin D deficiency rate in winter was higher than that in spring,summer and autumn(6.60％,2.64％,1.91％,1.66％).and the differences were statistically significant(x2=31.733,52.252,57.756,all P＜0.01).Conclusion A high incidence of vitamin D deficiency or insufficiency was found in children aged 3 to 6 in Hanzhong city.It was necessary to strengthen outdoor activities in winter,encourage monitoring of serum vitamin D levels,and supplement vitamin D if necessary.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

[摘 要] 目的：探讨肿瘤坏死因子受体相关蛋白1（TRAP1）在结肠癌组织和细胞中的表达及其与临床病理特征和患者预后的关系和相关分子机制。方法：通过TCGA和GEO数据全面分析TRAP1在结肠癌中的表达及其与临床病理特征和患者预后的关系，选取2020年10月至2021年03月间在山西医科大学第一医院手术切除的10例结肠癌组织及相应癌旁组织标本，用IHC染色法检测中国人结肠癌组织中TRAP1的表达进行验证，运行R包（survival和survminer）进行Kaplan-Meier生存分析；在线分析TRAP1蛋白的信号肽及穿膜结构域，通过基因富集分析软件进行GO分析和KEGG分析。培养结肠癌SW480和SW620细胞，将si-NC和si-TRAP1转染结肠癌细胞，实验分为空白对照组、si-NC组和si-TRAP1组，采用qPCR法检测转染后各组结肠癌细胞中TRAP1的表达，FCM检测转染后各组细胞的细胞周期和凋亡情况。结果：与癌旁组织比较，TRAP1在结肠癌组织中呈高表达（P<0.01），TRAP1表达水平与淋巴结转移有关联（P<0.05），TRAP1高表达组结肠癌患者5年OS率较低（P<0.05）。TRAP1蛋白属于细胞质蛋白，功能富集结果显示TRAP1及其相关分子与细胞周期、核糖体生物发生等信号通路有关（均P<0.01），TRAP1高表达组的结肠癌代谢重编程基因簇和线粒体蛋白输入基因簇水平升高（均P<0.01）。敲减TRAP1后，结肠癌细胞周期阻滞于G1期，细胞凋亡水平显著升高（均P<0.01）。结论：TRAP1在结肠癌组织中呈高表达，且与患者淋巴结转移和低OS率相关联，敲减TRAP1可阻滞结肠癌细胞周期并促进其凋亡。

Objective:To explore the value of different machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features in preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods:The data of 132 patients with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 72 cases of positive MVI and 60 cases of negative MVI. According to the proportion of 7∶3, the cases were randomly divided into training set and validation set. The radiomics features of hepatobiliary phase images for HCC were extracted by PyRadiomics software. The clinical and radiomics features of the training set were screened by the least absolute shrinkage and selection operator (LASSO) regression with 5 fold cross-validation, and then the optimal feature subset was obtained. Six machine learning algorithms, including decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model (GLM) and neural network, were used to build the prediction models, and the ROC curves were used to evaluate the prediction ability of the models. DeLong test was used to compare the differences of area under the curve (AUC) for 6 machine learning algorithms.Results:Totally 14 features selected by LASSO regression were obtained to form the optimal feature subset, including 2 clinical features (maximum tumor diameter and alpha-fetoprotein) and 12 radiomics features. The AUCs of decision tree, extreme gradient boosting, random forest, SVM, GLM and neural network based on the optimal feature subset were 0.969, 1.000, 1.000, 0.991, 0.966, 1.000 in the training set and 0.781, 0.890, 0.920, 0.806, 0.684, 0.703 in the validation set, respectively. There were significant differences in the AUCs between extreme gradient boosting and GLM or neural network ( Z=2.857, 3.220, P=0.004, 0.001). The differences in AUCs between random forest and SVM, GLM, or neural network were significant ( Z=2.371, 3.190, 3.967, P=0.018, 0.001,<0.001). The difference in AUCs between SVM and GLM was statistically significant ( Z=2.621 , P=0.009). There were no significant differences in the AUCs among the other machine learning models ( P>0.05). Conclusion:Machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features can be used to preoperatively predict MVI of HCC, particularly the extreme gradient boosting and random forest models have high prediction efficiency.

Objective:To investigate the value of pericoronary adipose tissue histogram parameters based on coronary CT angiography (CTA) images for the differentiation of acute coronary syndrome and stable coronary artery disease.Methods:The clinical data and CTA images of 93 patients with coronary CTA examination in Suzhou Kowloon Hospital from 2013 to 2018 were analyzed retrospectively. There were 39 patients with acute coronary syndrome (acute coronary syndrome group) and 54 patients with stable coronary artery disease (stable coronary artery disease group). A region of interest (ROI) was drawn around the stenosis of the coronary arteries, with CT attenuation ranging from-190 to -30 HU to exclude non-adipose tissue. The CT attenuation of ROI excluding non-adipose were measured and histogram analysis was performed. The obtained parameters included the mean value, median value and the 5th, 10th, 45th, 55th, 70th and 95th percentiles. The differences in histogram parameters between the two groups were compared, and then the value of each parameter in differentiating acute coronary syndrome and stable coronary artery disease was evaluated based on receiver operating characteristic (ROC) analysis. The stepwise regression of multivariate logistic regression analysis was used to identify the useful features and establish the final prediction model. The ROC curve of the final model was calculated and its value was analyzed.Results:The mean, median and the 5th, 10th, 45th, 55th,70th and 95th percentile differences between the acute coronary syndrome group and the stable coronary artery disease group were statistically significant (all P<0.05). The ROC curve for the median and the 95th percentile had the same area under curve (AUC) of 0.73. The sensitivity, specificity and AUC of the diagnostic model established by multiple logistic regression were 82.1%, 89.1% and 0.90 respectively. Conclusion:CT attenuation histogram of pericoronary adipose tissue is of high value in differentiating acute coronary syndrome from stable coronary artery disease.

Objective:To explore the value of gadolinium-ethoxybenzyl- diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI nomogram model for preoperative prediction of Ki-67 expression in hepatocellular carcinoma (HCC).Methods:Data of 85 patients of HCC confirmed by postoperative pathology, who underwent preoperative Gd-EOB-DTPA enhanced MRI between September 2016 and August 2019 in the First Affiliated Hospital of Soochow University were retrospectively evaluated. According to postoperative immunohistochemistry Ki-67 index, the 85 patients were divided into Ki-67 low expression group(Ki-67 index ≤10%, n=20) and Ki-67 high expression group (Ki-67 index >10%, n=65). Clinical data (hepatitis, cirrhosis, etc.), qualitative imaging parameters (tumor margin, capsule, etc.) were compared by χ 2 test and quantitative parameters [lesion-to-normal parenchyma ratio-arterial phase (LNR-AP), lesion-to-normal parenchyma ratio-portal phase (LNR-PP), lesion-to-normal parenchyma ratio-equilibrium phase (LNR-EP) and lesion-to-normal parenchyma ratio-hepatobiliary phase (LNR-HBP)] were compared by independent sample t test. The above statistically significant parameters were included in multivariate logistic regression to identify the independent predictors of Ki-67 high expression and then the nomogram model for predicting Ki-67 expression of HCC was established. Results:alpha-fetoprotein (AFP) tumor margin, arterial rim enhancement between the Ki-67 low expression group and the Ki-67 high expression group had significant differences (χ 2 were 8.196, 10.538 and 4.717, respectively, P<0.05). LNR-AP, LNR-PP, LNR-EP and LNR-HBP between the two groups had significant differences ( t were 2.929, 2.773, 2.890 and 3.437, respectively, P<0.05).The result of multivariate logistic regression revealed that AFP≥20 μg/L, non-smooth tumor margin and low LNR-HBP were the independent predictors of Ki-67 high expression (odds ratio were 4.090, 3.509 and 0.042, respectively, P<0.05).The Gd-EOB-DTPA enhanced MRI nomogram model for predicting Ki-67 expression of HCC was established successfully. The Area under the receiver operating characteristic curve of the nomogram was 0.837 and the corrected predictive curve fitted the ideal curve, which suggested the model had a good predictive efficiency. Conclusion:Gd-EOB-DTPA enhanced MRI nomogram model has great value in preoperative prediction of Ki-67 expression of HCC, which provided a personalized prediction method for Ki-67 expression in patient with HCC.

Objective To investigate the metabolic characteristics,body composition and dietary intake in elderly sarcopenia patients with type 2 diabetes(T2DM).Methods A total of 652 T2DM patients(327 males and 325 females)aged over 60 years were selected from endocrinology department of nine different hospitals in Beijing.Body composition was measured by bioimpedance analysis,and the appendicular skeletal mass index(ASMI)was calculated.Sarcopenia was defined as body height-adjusted skeletal muscle mass (ASMI)below the lower quintile of the young reference group.The diagnostic cutoff points for sarcopenia were 7.18 kg/m2 for men and 5.73 kg/m2 for women.All patients were divided into the sarcopenia group versus the control group(below vs.not below 7.18 kg/m2 for men and 5.73 kg/m2 for women).The anthropometric parameters,body composition,biochemical laboratory results and dietary intake were compared between the two groups.The blood glucose target levels were less than 7 mmol/L of fasting plasma glucose(FPG)or less than 7％ of haemoglobin A1c(HbA1c).The obesity ratio was calculated according to body fat percentage more than 25％ in men and more than 30％ in women as obesity.Results There were 116 (17.8％)patients in the sarcopenia group (men/women,82/34),and 536 (82.2 ％) patients in the control group (men/women,245/291).Age was higher in the sarcopenia group than in the control group(t =4.385,P =0.000),and body mass index and waist hip ratio(WHR)were lower in the sarcopenia group than in the control group(t =11.724 and 4.173,P=0.000 and 0.000).FPG[(7.5±2.4) mmol/L vs.(8.5±2.5)mmol/L,t =-3.450,P=0.001]and HbA1c[(7.0±1.6) ％ vs.(8.2± 1.7) ％,t =-5.745,P =0.000] were higher in male sarcopenia group than in male control group.The control rate of FPG (127.0％ or 51.8％ vs.27.0％ or 32.9％,x2=8.817,P=0.003)and HbA1c(131.0％ or 53.5％ vs.23.0％ or 28.0％,x2 =15.934,P=0.000)were lower in the sarcopenia group than in the control group.The red blood cell counts,hemoglobin and serum albumin levels,estimated glomerular filtr ationrate(eGFR)were lower in male sarcopenia group than in the male control group(P＜0.05).eGFR was lower in female sarcopenia group than in female control group(t =4.090,P =0.000).Both in men and women,ASMI,grip power,fatless circumference on upper arm,bone mineral content and basal metabolic rate were lower in the sarcopenia group than in the control group(P＜0.05).The total daily intake of energy,carbohydrate,protein and fat were lower in male sarcopenia group than in male control group(P＜ 0.05).Conclusions Compared with the control group,sarcopenia patients are older with worse glycemic control and lower levels of BMI,WHR,renal function,muscle mass and muscle strength.Sarcopenia patients are more prone to osteoporosis.Furthermore,they have poorer nutritional status with an imbalance of dietary intake.Appropriate increase of protein especially high quality protein intake should be recommended to sarcopenia patients with T2DM.

Objective To investigate the causes of peripheral cytopenia in patients with posthepatitic cirrhosis and portal hypertensive splenomegaly.Methods The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia who were operated in our hospital in the past 17 years were retrospectively studied.Results All these patients underwent splenectomy.Before operation,all these patients had one or more types of peripheral cytopenia (cumulative cytopenia:390 patient-times).After splenectomy,blood counts in 79.2％ returned to normal;in 15.9％ increased but failed to reach normal levels;and in 4.9％ became lower than before operation.5 patients died soon after operation.Conclusion Hypersplenism is the main cause for the peripheral cytopenia most cirrhotic portal hypertension patients.Splenectormy is an effective method to treat hypersplenism.

Aim To investigate the effect of SM-1 on seven main cytochrome P450(CYP450)in human liver microsomes.Methods Substrate or SM-1 was incubated with human liver microsomes for 30 min in vitro,and divided into control group and experimental group.The effects of SM-1 on the main phase I metabolic enzymes in human liver microsomes was detected by HPLC.Phenacetin,bupropion,paclitaxel,tolbutamide,omeprazole,dextromethorphan,testosterone were investigated as probe drugs.Results Inhibition rate of SM-1 on the classical substrate of human liver microsomal CYP was 0.05％,3.37％,0.08％,2.07％,4.20％,-0.15％and 10.84％,respectively.Conclusions SM-1 may have inhibitory effect on CYP3A4.Attention should be paid to the interaction of clinical drug induced by CYP enzyme inhibition.