Background: MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed. Methods: We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared. Results: Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM. Conclusion We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.

Objective:To prepare a peptide fluorescent probe based on aggregation-induced emission and to investigate its application in the detection of early caries.Methods:Eight aspartate-serine-serine (DSS) were combined with aggregation-induced emission material to prepare peptide fluorescent probes, and an artificial demineralization model was established in vitro. The samples were immersed in the peptide fluorescent probe solution for 1 min, and a fluorescence imaging system was applied to examine the tooth samples and collect images and fluorescence data. Scanning electron microscopy was also applied to observe the phenotype of the teeth, and electron microscopy was applied to detect the calcium-phosphorus ratio on the enamel surface of the teeth. Polarized light microscopy was also applied to observe the enamel area of the teeth. Results:The fluorescence intensity of demineralized teeth was clearly observed to be lower than that of normal teeth in the peptide fluorescent probe-treated area, and the difference was statistically significant ( P < 0.05). The results of scanning electron microscopy showed that the enamel surface of the demineralized group had more irregular pores, while the enamel surface of the undemineralized group was flatter with only some irregular accumulation of flakes. The results of polarized light microscopy showed that a clear birefringence could be observed in the enamel region of normal teeth, while a black area or the disappearance of the birefringence effect accompanied by a partial black dark shadow could be observed in the enamel region of demineralized teeth. Conclusions:An aggregation-induced luminescence-based peptide fluorescent probe was successfully prepared, which can precisely localize the enamel and show some application value in early caries detection.

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Objective:To investigate the application value of preoperative clinical and magnetic resonance imaging (MRI) targetoid enhancement combined with alpha-fetoprotein in evaluating the expression of cytokeratin 19 (CK19) in patients undergoing radical resection for single hepatocellular carcinoma (HCC) without macrovascular invasion.Methods:The retrospective cohort study was conducted. The clinicopathological data of 220 patients who underwent radical resection for single HCC without macrovascular invasion in the General Hospital of Ningxia Medical University from January 2016 to December 2020 were collected. There were 171 males and 49 females, aged (56±11)years. Of the 220 patients, 52 cases showed positive CK19 expression, while 168 cases showed negative CK19 expression. Observation indicators: (1) MRI and immunohistochemical staining results of patients with different status of CK19 expression; (2) comparison of clinical features of patients with different status of CK19 expression; (3) comparison of MRI features in patients with different status of CK19 expression; (4) analysis of influencing factors for CK19 expression in patients and predictive value. The normality of continuous variables was tested using the Shapiro-Wilk test. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were expressed as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers and (or) percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The relevant clinical and imaging features with P<0.05 were included in the binary Logistic regression model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the predictive efficiency of the model. Results:(1) MRI and immunohistochemical staining results of patients with different status of CK19 expre-ssion. Results of MRI examination in patients with positive CK19 expression showed the tumors with low-signal intensity on plain T1-weighted imaging, annular high enhancement in the arterial phase, clear boundaries in the portal venous phase, central enhance-ment in the delayed phase and targetoid high signals on diffusion-weighted imaging (DWI). Immuno-histochemical staining revealed a positive CK19 expression. Results of MRI examination in patients with negative CK19 expression showed the tumors with low-signal intensity on plain T1-weighted imaging, non-annular high enhancement in the arterial phase, unclear boundaries in the portal venous phase, low signals compared with peripheral liver tissue in the delayed phase and uniform high signals on DWI. Immunohistochemical staining revealed a negative CK19 expression. (2) Clinical features of patients with different status of CK19 expression. The neutrophil count and cases with alpha-fetoprotein (AFP) ≥400 μg/L were 3.07(2.21,4.41)×10 9/L and 26 in patients with positive CK19 expression, versus 2.72(2.05, 3.51)×10 9/L and 48 in patients with negative CK19 expression, showing significant differences between them ( Z=?2.06, χ2=8.17, P<0.05). (3) Compari-son of MRI features in patients with different status of CK19 expression. Cases with tumor diameter ≥ 5 cm and cases with tumor showing targetoid enhancement were 34 and 22 in patients with positive CK19 expression, versus 82 and 24 in patients with negative CK19 expression, showing significant differences between them ( χ2=4.38, 18.86, P<0.05). (4) Analysis of influencing factors for CK19 expression in patients and predictive value. Results of multivariate analysis showed that AFP ≥ 400 μg/L and targetoid enhance-ment were independent risk factors for positive CK19 expression in HCC patients [ odds ratio=2.09, 3.23, 95% confidence interval ( CI) as 1.06?4.13, 1.49?6.99, P<0.05]. Results of ROC curve analysis showed that the AUC of targetoid enhancement for predicting positive CK19 expression was 0.64 (95% CI as 0.57?0.71), with the sensitivity and specificity as 42.31% and 85.71%. The AUC of AFP ≥400 μg/L for predicting positive CK19 expression was 0.61 (95% CI as 0.53?0.68), with the sensitivity and specificity as 51.00% and 71.43%. The AUC of targetoid enhancement combined with AFP ≥400 μg/L for predicting positive CK19 expression was 0.69 (95% CI as 0.61?0.77), with the sensitivity and specificity as 67.31% and 63.10%, respectively. Conclusions:Targetoid enhancement and AFP ≥400 μg/L are independent risk factors for positive CK19 expression in patients with single HCC without macrovascular invasion. Their combination has clinical value for preoperative evaluation of CK19 expression.

GuiLingJi(GLJ),a classic traditional Chinese medicine(TCM)formula,is composed of over 20 herbs,according to the Pharmacopeia of the People's Republic of China.Owing to its various activities,GLJ has been used in clinical settings for more than 400 years in China.However,the ambiguous chemical material basis limits the development of studies on the quality control and pharmacological mechanisms of GLJ.Therefore,comprehensive characterization of the multiple chemical components of GLJ is of great significance for the modernization of this formula.Given the great variety of herbs in GLJ,both UHPLC-MS and 1H NMR techniques were employed in this study.In addition,solvent extraction with different polarities was used to eliminate signal interference and the concentration of trace components.A variety of MS analytic methods were also used,including implementation of a self-built compound database,diagnostic ion filtering,mass defect filtering,and Compound Discoverer 3.0 analysis software.Based on the above strategies,a total of 150 compounds were identified,including 5 amino acids,13 phenolic acids and glycosides,11 coumarins,72 flavones,20 triterpenoid and triterpenoid saponins,23 fatty acids,and 6 other compounds.Moreover,13 compounds were identified by 1H NMR spectroscopy.The UHPLC-MS and 1H NMR results supported and complemented each other.This strategy provides a rapid approach to analyzing and identifying the chemical composition of Chinese herbal prescriptions.The current study provides basis for further research on the quality control and pharmacological mechanism of GLJ.

Objective:To investigate the relationship between tube voltage kV value for head and neck CT angiography and body weight.Methods:A total of 120 patients with suspected vascular disease of the head and neck who underwent CT angiography of the head and neck in Beihai People's Hospital from January 2020 to May 2022 were included in this study. Patients were divided into three groups according to different tube voltages: group A (tube voltage 120 kV, n = 45), group B (tube voltage 100 kV, n = 45) and group C (tube voltage 80 kV, n = 30). Patients in group A were divided into group A1 (< 70 kg, n = 15), group A2 (70-85 kg, n = 15) and group A3 (> 85 kg, n = 15) according to different body weights. Patients in group B were divided into group B1 (< 70 kg, n = 15), group B2 (70-85 kg, n = 15) and group B3 (> 85 kg, n = 15) according to different body weights. Patients in group C were divided into group C1 (< 70 kg, n = 15) and group C2 (70-85 kg, n = 15) according to different body weights. Group C3 was not used. The contrast medium used was Loversol. The CT value, image noise, signal-to-noise ratio, contrast to noise ratio, and effective radiation dose of arterial vessels in each group were measured. The images were subjectively evaluated by two physicians who had senior professional titles using a 5-point rating scale. Results:Subjective score of image quality was all ≥ 3 grade in each group. There was no significant difference in image quality rating between groups A1 and A2 and groups B1, B2, and C1. There was a remarkable difference in image quality rating between groups A3, B3, and C2 and the other groups. There was a significant difference in the CT value of blood vessels at four different levels between groups A1, B1 and C1 ( F = 76.82, 64.62, 98.79, 71.85, all P < 0.001). There was a significant difference in CT value of blood vessels at four different levels between groups A2, B2 and C2 ( F = 159.82, 112.33, 108.22, 135.18, all P < 0.001). There was a significant difference in CT value of blood vessels at four different levels between groups A3 and B3 ( t = 4.40, 4.27, 3.91, 3.59, all P < 0.05). In groups B3 and C2, the image noise was remarkably increased, signal to noise ratio and contrast to noise ratio were remarkably decreased compared with those in the other groups. The effective radiation dose of arterial vessels in group B1 was 47% lower than that in group A1 and the effective radiation dose of arterial vessels in group C1 was 73% lower than that in group A1 ( F = 116.18, P < 0.001). The effective radiation dose of arterial vessels in group B2 was 49% lower than that in group A2, and the effective radiation dose of arterial vessels in group C2 was 66% lower than that in group A2 ( H = 35.40, P < 0.001). The effective radiation dose in group B3 was 35% lower than that in group A3 ( t = 3.59, P < 0.05). Conclusion:In CT angiography of the head and neck, the selection of tube voltage kV value is related to body weight. Tube voltage 80 kV is suitable for patients with a body weight < 70 kg, tube voltage 100 kV for patients with a body weight of 70-85 kg, and tube voltage 120 kV for patients with a body weight > 85 kg. These tube voltages can decrease effective radiation dose and ensure image quality, meeting the requirement for clinical diagnosis.

Objective:To explore the value of clinical data and MRI image features in predicting and analyzing the degree of differentiation of hepatocellular carcinoma (HCC).Methods:The clinical and imaging data of 180 patients with surgical outcomes of HCC from March 2015 to June 2019 in the General Hospital of Ningxia Medical University were retrospectively analyzed. Alpha-fetoprotein (AFP)、aspartate aminotransferase (AST)、D-dimer、clinical stage、tumor length、apparent diffusion coefficient(ADC)、enhancement types and so on the clinical and imaging data of the poorly differentiated and non-differentiated HCC were compared and analyzed. Multivariate logistic regression was used to predict independent risk factors for poorly differentiated HCC.Results:Of the 180 HCC patients, 121 were moderately and highly differentiated, and 59 were poorly differentiated. Univariate analysis showed that the patient’s age, gender, AFP, AST, D-dimer level, clinical stage, Child-Pugh score, tumor length, whether the capsule was complete, tumor apparent diffusion coefficient, the maximum level ADC value, enhancement type with HCC differentiation degree were correlated(all P<0.05). Multivariate logistic regression analysis showed that the patients' gender ( OR=4.524, P<0.05), clinical stage ( OR=5.598, P<0.05), D-dimer ( OR=8.576, P<0.05), HCC diameter ( OR=0.498, P<0.05), enhancement types ( OR=2.988, P<0.05), tumour ADC value ( OR=0.059, P<0.05) were independent of poorly differentiated HCC risk factor. Conclusion:MRI image features can be used as an effective indicator to predict the degree of HCC differentiation before surgery. It is more valuable to accurately predict the degree of HCC combined with D-dimer and AFP value.

Objective:To analyze the imaging features of spontaneous rupture of primary liver cancer (PLC) and to study the high-risk factors associated with tumor rupture.Methods:From September 2016 to August 2020, 81 patients who developed spontaneous rupture of PLC at the General Hospital of Ningxia Medical University were included into this study. A control group of 81 patients with tumors located on the periphery of the liver but without rupture treated in the same period were selected by matching the two groups with age, sex and BCLC staging. The clinical data and CT imaging characteristics including tumor location, extent, size, and morphology of the two groups of patients were compared retrospectively between groups.Multivariate logistics regression was used to analyze.Results:A total of 81 patients were included in the case group, including 72 males and 9 females, aged (53.69±10.34) years. The control group included 81 patients, 64 males and 17 females, aged (54.78±9.04) years. The main risk factors for spontaneous rupture of PLC included in this study were cirrhosis, tumor close to diaphragm, biolobar distribution, portal vein obstruction, tumor diameter >10 cm, invasion of liver capsule (arc-to-chord ratio>1) and tumor protrusion ≥25% ( P<0.05). Logistic regression analysis showed that cirrhosis ( OR=2.796, 95% CI: 1.721-10.834), portal vein obstruction ( OR=3.586, 95% CI: 1.272-10.107) and tumor protrusion (≥25%) ( OR=2.831, 95% CI: 1.668-22.210) were independent predictive factors of spontaneous rupture of PLC. Conclusion:Tumor protrusion≥25%, cirrhosis and portal vein obstruction were closely related to spontaneous rupture of PLC. They were independent risk factors in predicting rupture of primary liver cancer.