Objective To explore whether liver cirrhosis markers aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4 index(FIB-4)based on blood biochemical indicators can predict disease free survival(DFS)and overall survival(OS)in patients with hepatocellular carcinoma(HCC)after resection.Methods 300 patients with HCC who underwent radical resection in Zhongshan Hospital,Fudan University from February 2005 to July 2017 were enrolled and the clinicopathological characteristics,recurrence and survival of these patients were retrospectively collected.The relationships between APRI,FIB-4 and postoperative recurrence and survival were evaluated.The ROC curve was used to evaluate the predictive values of APRI,FIB-4.Results The median follow-up of 300 patients was 61 months.Univariate Cox regression analysis showed that APRI,FIB-4,vascular invasion were risk factors affecting postoperative DFS and OS.The multivariate Cox regression analysis showed that vascular invasion was the independent risk factor for postoperative DFS(HR=1.518,95%CI 1.024-2.252,P=0.038)and OS(HR=2.301,95%CI 1.270-4.167,P=0.006).The time dependent ROC(time-ROC)curve showed that AUCs of APRI and FIB-4 predicting 1-year,3-year,and 5-year DFS were 0.555-0.596,which were 0.600-0.679 when predicting 1-year,3-year,and 5-year OS.Conclusions The predictive value of APRI and FIB-4 based on blood biochemical indicators alone for postoperative DFS and OS in HCC patients is limited.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective:To explore the uptake characteristics and temporal changes of 68Ga-fibroblast activation protein inhibitors (FAPIs) and 18F-FDG in the anastomotic site of reconstructed digestive tracts after radical surgery for gastrointestinal adenocarcinoma. Methods:A cohort of 43 patients (28 males, 15 females; age range 28-79 years) who underwent radical surgery for gastrointestinal adenocarcinoma and underwent 18F-FDG PET/CT follow-up between November 2020 and June 2022 in the First Affiliated Hospital of the Air Force Medical University was prospectively included. One week after the 18F-FDG PET/CT examination, 68Ga-FAPI-04 PET/CT imaging was performed. ROIs were drawn on the PET images at the highest uptake level of anastomotic sites of reconstructed digestive tract and abdominal wall incisions, and SUV max and target-to-background ratio (TBR) were determined. χ2 test, one-way analysis of variance, Kruskal-Wallis rank sum test (Bonferroni correction) and Wilcoxon signed-rank test were supplied. Results:There were 86 surgical wounds (13 gastric-intestinal anastomotic sites, 14 esophagus-intestinal anastomotic sites, 16 intestinal-intestinal anastomotic sites, and 43 abdominal wall incisions) included. In 68Ga-FAPI-04 PET imaging, SUV max of gastric-intestinal anastomotic sites was higher than that of abdominal wall incisions, with a statistically significant difference (adjusted P=0.014). The TBR did not show statistically significant differences among different types of surgical wounds ( H=3.88, P=0.275). In 18F-FDG PET imaging, SUV max of gastric-intestinal, esophagus-intestinal, and intestinal-intestinal anastomotic sites were all higher than that of abdominal wall incisions, with statistically significant differences (adjusted all P<0.001). There were no statistically significant differences in TBR among different types of surgical wounds ( H=3.02, P=0.388). In 68Ga-FAPI-04 PET imaging, the TBR of all types of anastomotic sites exhibited a decreasing trend with increasing postoperative time. Except for intestinal-intestinal anastomotic sites, the differences in TBR between < 0.5-year and ≥ 1.5-year groups were statistically significant for other types of surgical wounds (adjusted P<0.05). In 18F-FDG PET imaging, the TBR of abdominal wall incisions showed a decreasing trend with increasing postoperative time. However, the TBR of other types of surgical wounds did not show a decreasing trend, and the differences in TBR among different time groups were not statistically significant ( H values: 0.53-2.75, P values: 0.252-0.768). In comparing the two PET imaging agents, for all surgical wounds within the <0.5-year and 0.5-1.5-year groups, the 68Ga-FAPI-04 TBR was consistently higher than the 18F-FDG TBR ( z values: -3.17 and -2.55, P values: 0.002 and 0.011). However, in the ≥1.5-year group, the TBR values tended to be consistent, and the differences were not statistically significant ( z=-0.70, P=0.485). Conclusions:The 18F-FDG uptake in the anastomotic sites of reconstructed digestive tracts reaches a low level under half a year after surgery and does not significantly change over time, while the 68Ga-FAPIs uptake remains relatively high within the first 1.5 years after surgery but decreases over time. These patterns suggest that clinical attention should be paid to the differential diagnosis of anastomotic inflammation or fibrosis, which resulting in agent uptake and local tumor recurrence.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate （HD-MTX） and the occurrence of adverse drug reactions （ADR） when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021， the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis， such as medical record number， age， sex， height， body mass， chemotherapy plan， dosage； test indexes such as alanine transaminase， aspartate transaminase， total bilirubin， creatinine clearance （CrCl）， albumin （ALB） and other indexes were also collected before and after administration. The blood concentrations （c6 h， c24 h， c48 h） of HD-MTX were recorded， drug information of proton pump inhibitors （PPIs） was extracted and used， and ADR occurring within 48 h after administration were all evaluated. Single factor analysis， multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age， CrCl had an effect on c 6 h （P＜0.05）； age， CrCl and ALB had an effect on c24 h （P＜0.05）； age， body mass index （BMI）， CrCl， combined use of PPIs and ALB had an effect on c48 h （P＜0.05）. The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h （P＞0.05）， age was the main influential factor of c 24 h （P＜0.05）， and CrCl and combined use of PPIs were the main influential factors of c48 h （P＜0.05）； the coefficient of variance expansion was between 1 and 3.5， indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%， of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age， BMI， liver function and CrCl had effect on the incidence of ADR （P＜0.05）. CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma， the patient’s age， CrCl and combined use of PPIs should be considered， and the patient’s blood concentration should be monitored； at the same time， the age of patients， BMI， liver function and CrCl have an impact on the incidence of ADR.

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)-CreER-p65^f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Objective:To investigate the feasibility and clinical value of MRI quantitative evaluation technique in detecting sternocleidomastoid muscle fibrosis in patients with nasopharyngeal carcinoma (NPC) after radiotherapy.Methods:From August 2019 to March 2021, 45 patients with clinically confirmed NPC after radiotherapy and 30 healthy controls who underwent physical examination in Lishui Hospital of Zhejiang University were enrolled in our study. According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) classification criteria of late radiation reactions respectively, the sternocleidomastoid muscle injury in the NPC group was divided into grade Ⅰ, Ⅱ and Ⅲ, which included 8, 32 and 5 patients respectively. All patients underwent T 1 mapping and T 2 mapping imaging of the neck. Firstly, the mapping images of sternocleidomastoid muscle between the two groups were analyzed and compared. Using NUMARIS/4 software of Siemens image post-processing workstation, the region of interest was manually drawn along the edge of sternocleidomastoid muscle at the level of laryngeal chamber in axial mapping diagram. Then, T 1 and T 2 values and the long and short diameters of sternocleidomastoid muscle were measured respectively. Finally, the differences of the parameters between the two groups were compared by independent sample t-test, Spearman rank correlation was used to analyze the relationship between the average T 1 and T 2 values of bilateral sternocleidomastoid muscles and the grade of late radiation injury. Results:Compared with the control group, the shape of sternocleidomastoid muscle in the NPC group was smaller in shape, with irregular edge and uneven increase of T 1 mapping color scale. There was no significant difference in muscle signal in T 2 mapping. The T 1 values of left and right sternocleidomastoid muscles in the NPC group were (1 524.7±97.6) and (1 496.5±93.2) ms respectively, which were significantly higher than those in the normal control group [(1 231.5±85.3) and (1 275.9±90.9) ms] ( P<0.05), and the T 2 values of left and right sternocleidomastoid muscles in the NPC group were (28.4±4.8) and (28.4±3.6) ms respectively, which were lower than those in the normal control group [(30.4±3.5) and (30.4±3.5) ms] ( P<0.05). The long and short diameters of bilateral sternocleidomastoid muscles in the NPC group were shorter than those in the control group ( P<0.05). The average T 1 and T 2 values of bilateral sternocleidomastoid muscles in NPC patients after radiotherapy were (1 510.6±95.4) and (28.4±4.2) ms respectively, The T 1 value was positively correlated with the classification of advanced radiation injury ( r=0.78, P<0.001), and T 2 value was negatively correlated with the level of advanced radiation injury ( r=-0.87, P<0.001). Conclusion:Mapping quantitative evaluation technique can noninvasively and objectively detect and evaluate sternocleidomastoid muscle fibrosis after NPC radiotherapy, which has potential clinical application value.

Objective:To exploring the uptake of fibroblast activation protein (FAP) inhibitor (FAPI) in pancreatic cancer through 68Ga-FAPI-04 PET/CT imaging, and provide a basis for the FAP-targeted imaging of pancreatic cancer. Methods:Pancreatic cancer-patient-derived tumor xenograft (PDX) mouse models ( n=8) were developed, then 68Ga-FAPI-04 and 18F-FDG microPET/CT imaging were performed (4 in each group). The differences of percentage activity of injection dose per gram of tissue (%ID/g) of 68Ga-FAPI-04 and 18F-FDG were analyzed by independent-sample t test. 68Ga-FAPI-04 and 18F-FDG PET/CT imaging were performed in 5 patients (4 males, 1 female, age: 46-74 (63.0±11.9) years) with pancreatic cancer, and the maximum standardized uptake value (SUV max) of 68Ga-FAPI-04 and 18F-FDG in primary pancreatic cancer and the SUV max ratio of liver metastases to liver tissue were compared by paired t test. Results:MicroPET/CT imaging showed that 68Ga-FAPI-04 was obviously uptaken at all time points in the tumor of PDX mice. The uptake of 68Ga-FAPI-04 in PDX mice 60 min after injection was significantly higher than that of 18F-FDG ((6.58±0.44) and (4.29±0.13) %ID/g; t=4.152, P=0.008 9). PET/CT showed that the SUV max of 68Ga-FAPI-04 in pancreatic cancer was significantly higher than that of 18F-FDG (16.82±3.08 and 5.14±2.20; t=6.893, P=0.000 1) and the SUV max ratio of liver metastases to liver tissue of 68Ga-FAPI-04 was also significantly higher than that of 18F-FDG (4.57±1.47 and 1.30±0.16; t=3.803, P=0.019 1). Conclusion:68Ga-FAPI-04 can be highly uptaken in pancreatic cancer, suggesting that FAP can be a potential target for PET/CT imaging of pancreatic cancer.

The electronic stethoscope combined with artificial intelligence (AI) technology has realized the digital acquisition of heart sounds and intelligent identification of congenital heart disease, which provides objective basis for heart sound auscultation and improves the accuracy of congenital heart disease diagnosis. At the present stage, the AI based cardiac auscultation technique mainly focuses on the research of AI algorithms, and the researchers have designed and summarized a variety of effective algorithms based on the characteristics of cardiac audio data, among which the mel-frequency cepstral coefficients (MFCC) is the most effective one, and widely used in the cardiac auscultation. However, the current cardiac sound analysis techniques are based on specific data sets, and have not been validated in clinic, so the performance of algorithms need to be further verified. The lack of heart sound data, especially the high-quality, standardized, publicly available heart sound database with disease labeling, further restricts the development of heart sound diagnostic analysis and its application in screening. Therefore, expert consensus is necessary in establishing an authoritative heart sound database and standardizing the heart sound auscultation screening process for congenital heart disease. This paper provides an overview of the research and application status of auscultation algorithm and hardware equipment based on AI in auscultation screening of congenital heart disease, and puts forward the problems to be solved in clinical application of AI auscultation screening technology.
Algorithms ; Artificial Intelligence ; Heart Auscultation/trends* ; Heart Defects, Congenital/diagnosis* ; Humans ; Mass Screening/methods*