Grape seed proanthocyanidins regulate mitophagy of endothelial cells and promote wound healing in mice through p-JNK/FOXO3a/ROS signal pathway.

Skin wound healing is a dynamic and complex process that involves multiple physiological and cellular events. Grape seed proanthocyanidins (GSP) have strong anti-oxidation and elimination of oxygen free radicals, and have been shown to significantly promote wound healing, but the underlying mechanism remains unclear. Studies have indicated that reactive oxygen species (ROS) acts as an upstream signal to induce mitophagy, suggesting that GSP can regulate mitophagy through the signal pathway. This study aimed to investigate whether GSP regulates mitophagy by down-regulating oxidative stress to promote wound healing. In vivo, GSP treatment accelerated wound healing, granulation tissue formation, collagen deposition, and angiogenesis in mice. Moreover, GSP down-regulated ROS levels and promoted the expression of antioxidant proteins by up-regulating the expression of p-JNK/FOXO3a protein, thereby regulating the expression of mitophagy-related proteins. In vitro, 4 µg/mL GSP showed no apparent toxic effects on cells and effectively reduce the oxidative stress damage of cells induced by H2O2. Western blot and superoxide anion fluorescence probe further confirmed that GSP effectively reduced Dihydroethidium content and up-regulated the expression of antioxidant proteins by activation of p-JNK/FOXO3a protein expression, thereby regulating mitophagy. Taken together, the findings from in vitro and in vivo experiments provide new insights into the promotion of wound healing by GSP.

Implementation of mind mapping with problem-based learning in prosthodontics course for Chinese dental students.

BACKGROUND: The traditional Chinese dentistry classroom teaching model focuses on the instruction of knowledge details, but less on the frameworks and learners' motivation. Here, we introduced a combination of mind mapping and PBL instruction (MBL)into the prosthodontics course for Chinese dental students. This study aimed to evaluate the effectiveness and efficiency of MBL in prosthodontics and make observations from the students' perspectives, based on their response with the learning process. METHODS: We prospectively enrolled 56 fourth-year undergraduates of stomatology, and these participants were randomly allocated into either the combined mind map teaching group (MBL) or the problem-based learning group (PBL) to attend the prosthodontics course. An anonymous questionnaire was also administered to both groups to evaluate the students' perceptions and experiences, using closed and open-ended items. Data were analyzed using descriptive statistics and thematic analysis. RESULTS: The students' responses to closed items indicate their experience in PBL and MBL to be positive, including increased motivation, improved memory of knowledge, enhanced discipline connection and raised teamwork, with fairly higher ratings for the MBL group. However, the tutor-guided competence scores including the memory and framework part, were significantly higher for MBL group than PBL group (two-way ANOVA, p < 0.01, p < 0.001, respectively). Meanwhile, the self-perceived competence scores including the motivation, framework and teamwork part, were significantly higher for MBL group than PBL group (two-way ANOVA, p < 0.01, p < 0.001, p < 0.05, respectively). CONCLUSION: Our findings suggest that MBL teaching approach can help in integration of knowledge structure and enhance clinical reasoning. MBL is an effective and well-organized method in prosthodontics course for dental students.

Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells.

Emerging evidence suggests that poor glycemic control mediates post-translational modifications to the H3 histone tail. We are only beginning to understand the dynamic role of some of the diverse epigenetic changes mediated by hyperglycemia at single loci, yet elevated glucose levels are thought to regulate genome-wide changes, and this still remains poorly understood. In this article we describe genome-wide histone H3K9/K14 hyperacetylation and DNA methylation maps conferred by hyperglycemia in primary human vascular cells. Chromatin immunoprecipitation (ChIP) as well as CpG methylation (CpG) assays, followed by massive parallel sequencing (ChIP-seq and CpG-seq) identified unique hyperacetylation and CpG methylation signatures with proximal and distal patterns of regionalization associative with gene expression. Ingenuity knowledge-based pathway and gene ontology analyses indicate that hyperglycemia significantly affects human vascular chromatin with the transcriptional up-regulation of genes involved in metabolic and cardiovascular disease. We have generated the first installment of a reference collection of hyperglycemia-induced chromatin modifications using robust and reproducible platforms that allow parallel sequencing-by-synthesis of immunopurified content. We uncover that hyperglycemia-mediated induction of genes and pathways associated with endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content.

Application of MLP neural network to predict X-ray spectrum from tube voltage, filter material, and filter thickness used in medical imaging systems.

The X-ray energy spectrum is crucial for image quality and dosage assessment in mammography, radiography, fluoroscopy, and CT which are frequently used for the diagnosis of many diseases including but not limited to patients with cardiovascular and cerebrovascular diseases. X-ray tubes have an electron filament (cathode), a tungsten/rubidium target (anode) oriented at an angle, and a metal filter (aluminum, beryllium, etc.) that may be placed in front of an exit window. When cathode electrons meet the anode, they generate X-rays with varied energies, creating a spectrum from zero to the electrons' greatest energy. In general, the energy spectrum of X-rays depends on the electron beam's energy (tube voltage), target angle, material, filter thickness, etc. Thus, each imaging system's X-ray energy spectrum is unique to its tubes. The primary goal of the current study is to develop a clever method for quickly estimating the X-ray energy spectrum for a variety of tube voltages, filter materials, and filter thickness using a small number of unique spectra. In this investigation, two distinct filters made of beryllium and aluminum with thicknesses of 0.4, 0.8, 1.2, 1.6, and 2 mm were employed to obtain certain limited X-ray spectra for tube voltages of 20, 30, 40, 50, 60, 80, 100, 130, and 150 kV. The three inputs of 150 Multilayer Perceptron (MLP) neural networks were tube voltage, filter type, and filter thickness to forecast the X-ray spectra point by point. After training, the MLP neural networks could predict the X-ray spectra for tubes with voltages between 20 and 150 kV and two distinct filters made of aluminum and beryllium with thicknesses between 0 and 2 mm. The presented methodology can be used as a suitable, fast, accurate and reliable alternative method for predicting X-ray spectrum in medical applications. Although a technique was put out in this work for a particular system that was the subject of Monte Carlo simulations, it may be applied to any genuine system.

Evaluation of Diagnostic Scores for Acute Appendicitis.

OBJECTIVE: To assess the sensitivity of the Alvarado score (AS), modified Alvarado score (MAS), Fenyo-Lindberg score (FS), Lintula score (LS), Eskelinen score (ES), Teicher score (TS), and Christian score (CS) [seven scorings] in patients with acute appendicitis (AA). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: The First Affiliated Hospital of Chongqing Medical University, China, from January 2012 to June 2015. METHODOLOGY: Patients with diagnosis of AA were evaluated retrospectively to compare the scoring systems. The diagnostic sensitivity (the correct number of diagnoses divided by the total number) was compared. Data were analyzed using SPSS software. RESULTS: One hundred and seventy-nine patients were studied. The sensitivity of AS was 92.7%; It outperformed each of the other scores. The sensitivity of FS, LS, and TS in women was lower than that in men (p=0.016, p<0.001, and p<0.001, respectively). The sensitivity of the FS, ES, TS, and CS in patients with a duration of illness greater than 48 hours was lower than that in patients with a duration of illness less than 48 hours (p<0.001 for all). CONCLUSION: AS is the most useful and sensitive diagnostic tool for AA. FS, LS, and TS had a lower diagnostic sensitivity in women; and FS, ES, TS, and CS had a low sensitivity in patients with a duration of illness greater than 48 hours.

Mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma cells / 国际肿瘤学杂志

Objective:To investigate the inhibitory effect and killing mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma (NK/TCL) .Methods:Human NK cell leukemia cell line YT and human NK/TCL cell line NK92 cells were treated with 0, 0.05, 0.10, 0.20, 0.30, 0.40, 0.50 μmol/L BDA-366. CCK-8 assay was used to calculate the half inhibitory concentration (IC 50) value of BDA-366 on these cells. The apoptosis levels of cells in control group and IC 50 BDA-366 treated group were detected by flow cytometry. Western blotting was used to detect the expression levels of apoptosis-related proteins in cells of control group and 1/2 IC 50, IC 50, 2× IC 50 BDA-366 treated groups. TMRE and Fluo-3 fluorescent probe were used to detect mitochondrial membrane potential of control group and IC 50 BDA-366 treated group, and the intracellular Ca 2+ concentration of control group, IC 50, 2× IC 50 BDA-366 treated groups. NOD-SCID mice in control group and 10 mg/kg BDA-366 intraperitoneal injection group were weighed and HE staining was performed to evaluate the toxicity of BDA-366 in vivo. Results:The IC 50 of BDA-366 for YT and NK92 cells were 0.065 and 0.086 μmol/L respectively. The apoptosis rates of YT cells in the control group and 0.065 μmol/L BDA-366 group were (6.62±1.59) % and (34.60±3.06) % respectively. The apoptosis rates of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were (5.57±0.88) % and (29.18±0.90) % respectively, both with statistically significant differences ( t=14.05, P<0.001; t=32.58, P<0.001). The relative expression of Bax in NK92 cells of the control group, 0.043, 0.086 and 0.172 μmol/L BDA-366 groups were 0.85±0.00, 1.26±0.04, 1.51±0.18, 1.15±0.10 ( F=20.70, P<0.001), the relative expression of Bax in BDA-366 groups were higher than that in the control group (all P<0.05). The fluorescence intensity of TMRE of YT cells in the control group and 0.065 μmol/L BDA-366 group were 8 372.00±330.47 and 6 419.67±311.34, and that of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were 9 169.00±535.72 and 7 311.67±295.52 respectively, and there were statistically significant differences ( t=7.45, P=0.002; t=5.26, P=0.006). In YT cells, the intracellular Ca 2+ concentrations of 0.065 and 0.130 μmol/L BDA-366 groups were significantly higher than that of the control group (5 791.67±220.45, 6 729.33±585.39, 4 874.67±112.61, F=19.16, P=0.003) ( P=0.039; P=0.002). In NK92 cells, the intracellular Ca 2+ concentrations of 0.086 and 0.172 μmol/L BDA-366 groups were significantly higher than that of the control group (4 553.67±17.62, 4 740.33±254.50, 4 185.67±17.67, F=10.96, P=0.010) ( P=0.039; P=0.007). There was no statistically significant difference in body weight change on day 12 compared with day 0 of NOD-SCID mice between BDA-366 group and control group [ (3.18±0.01) g vs. (2.73±0.58) g, t=0.60, P=0.570], and HE staining showed no abnormal morphology of heart, liver, spleen, lung and kidney in BDA-366 group. Conclusion:BDA-366 promotes NK/TCL cells apoptosis in vitro, but does not cause weight loss and morphological changes of organs by HE staining in vivo. The inhibitory effect of BDA-366 on NK/TCL cells may be achieved by increasing Bax expression, inducing Ca 2+ release and reducing mitochondrial membrane potential.

Study on the relationship between anti-gp210, anti-sp100 antibodies and clinical features and prognosis of patients with primary biliary cholangitis / 中华风湿病学杂志

Objective:To study the correlation between anti-gp210 antibody, anti-sp100 antibody with clinical features and prognosis of patients with PBC.Methods:A total of 992 patients with PBC from 9 medical centers in Yunnan Province from January 1, 2015 to December 31, 2021 were included retrospectively. The demographic data, medical history, UDCA treatment, laboratory and imaging data were collected, and telephone follow-up was conducted. The positive rates of anti-gp210 antibody and anti-sp100 antibody in PBC patients with different clinical characteristics were compared, and the differences of laboratory parameters and prognosis between the anti-gp210 and anti-sp100 antibodies positive and negative groups were compared. T test, rank sum test, variance analysis were used for statistical analysis.Results:The positive rate of anti-gp210 antibody in Han patients was significantly higher than that in minority patients (21.5% vs 9.9%, χ2=6.88, P=0.009), but there was no significant difference in the positive rate of anti-sp100 antibody between the two groups (10.9% vs 6.6%, χ2=1.62, P=0.204).There were no significant differences in the positive rates of anti-gp210 antibody and anti-sp100 antibody among different genders ( χ2=0.50, P=0.478)( Z=-0.41, P=0.682)and ages( χ2=0.01, P=0.951)( Z=-0.60, P=0.549). There was no significant difference in the positive rate of anti-gp210 antibody between AMA M2 antibody positive and negative patients ( χ2=3.45, P=0.063), PBC patients with Sj?gren′s syndrome compared with those without Sj?gren′s syndrome (21.3% vs 20.4%, χ2=0.05, P=0.828), and PBC patients with viral hepatitis compared with those without viral hepatitis(19.6% vs 20.5%, χ2=0.02, P=0.877). The positive rate of anti-gp210 antibody was significantly increased in patients with PBC confirmed by liver biopsy with unknown diagnosis (25.6% vs 18.4%, χ2=6.52, P=0.011), patients with AIH (26.6% vs 18.9%, χ2=5.82, P=0.016), cirrhosis (23.3% vs 11.3%, χ2=16.00, P<0.001), decompensation of cirrhosis (23.9% vs 18.2%, χ2=4.66, P=0.031), jaundice (29.7% vs 17.1%, χ2=18.59, P<0.001) and hyperlipidemia (24.9% vs 18.1%, χ2=6.30, P=0.012). The positive rate of anti-sp100 antibody was significantly increased in patients with negative AMA M2 antibody PBC patients (20.9% vs 7.2%, χ2=36.54, P<0.001)and patients with PBC confirmed by liver biopsy with unknown diagnosis (17.9% vs 7.5%, χ2=23.40, P<0.001), while in patients with AIH (11.1% vs 10.3%, χ2=0.09, P=0.769), Sj?gren′s syndrome (15.7% vs 10.0%, χ2=2.87, P=0.090), viral hepatitis (4.3% vs 10.8%, χ2=1.94, P=0.164), cirrhosis(10.5% vs 10.5%, χ2<0.01, P=0.991), decompensated symptoms of cirrhosis (10.3% vs 10.6%, χ2=0.03, P=0.868), jaundice (12.5% vs 9.7%, χ2=1.62, P=0.203)and hyperlipidemia (8.7% vs 11.5%, χ2=1.86, P=0.172), the positive rate was not significantly increased. The levels of ALT [71.00(48.00, 111.00)U/L vs 58.00 (31.00,112.75)U/L, Z=-2.63, P=0.009], AST [92.00 (54.00, 133.00)U/L vs 76.00(42.00, 128.00)U/L, Z=-2.73, P=0.006], ALP[306.00(176.00, 528.00)U/L vs 204.00(126.25, 350.75)U/L, Z=-4.78, P<0.001], GGT[284.00(131.00, 524.00)U/L vs 165.00(53.63, 389.00)U/L, Z=-4.36, P<0.001], TBIL[33.60(16.60, 82.10)mmol/L vs 23.45 (14.80, 61.13)mmol/L, Z=-3.00, P=0.003], DBIL [20.30 (6.60, 66.40)mmol/L vs 11.60 (5.90, 45.00)mmol/L, Z=-3.13, P=0.002], bile acid[53.40(19.50, 148.00)mmol/L vs 39.30(11.70, 118.58)mmol/L, Z=-2.26, P=0.024], IgM[3.61(2.03,5.26)g/L vs 2.39(1.37, 3.67)g/L, Z=-5.38, P<0.001] and APTT[37.40(33.10, 41.30)s vs 35.70 (31.30, 41.30)s, Z=-3.28, P=0.001])were significantly increased in patients with positive anti-gp210 antibody compared patients with negative anti-gp210 antibody, while the IgG level was significantly increased in patients with positive anti-sp100 antibody compared with patients with negative anti-gp210 antibody( Z=-2.25, P=0.025), but no other indexes were significantly increased. The Mayo risk score[3.48(2.46, 5.01) vs 3.18 (2.20, 4.64), Z=-2.052, P=0.04] and mortality at the end of follow-up (24.6% vs 16.7%, χ2=6.57, P=0.0.038)in patients with positive anti-gp210 antibody were much higher than those in patients with negative anti-gp210 antibody, but there were no significant differences in Mayo risk score [3.16 (2.21, 4.53) vs 3.28 (2.23,4.71), Z=-0.86, P=0.392] and mortality at the end of follow-up (13.5% vs 18.9%, χ2=2.12, P=0.346) between anti-sp100 antibody positive and negative patients. Conclusion:PBC patients with positive anti-gp210 antibody may have more serious liver pathologic damage and extra-hepatic complications, more serious liver function impairment, more obvious cholestasis, and worse prognosis. Anti-sp100 antibody has been shown to have no significant correlation with disease severity and prognosis.

Comparison of qualitative diagnostic value of 3 methods based on 18F-FDG PET-CT for solitary pulmonary nodules / 肿瘤研究与临床

Objective:To compare the value of 3 methods (threshold method, visual method and CT method) based on 18F-FDG PET-CT for qualitative diagnosis of solitary pulmonary nodules (SPN). Methods:The clinical characteristics, pathological results, CT signs and maximum standardized uptake value (SUV max) of 226 SPN patients who underwent 18F-FDG PET-CT and met lung imaging reporting and data system (Lung-RADS1.1) grading criteria grade 2-4 in Shanxi Province Cancer Hospital from January 2015 to January 2019 were retrospectively analyzed, and the diagnostic efficacy of threshold method (according to SUV max), visual method [according to the degree of fluorodeoxyglucose (FDG) uptake in the mediastinum or liver blood pool] and CT method (according to Lung-RADS1.1 grading criteria) for SPN were compared by using receiver operating characteristic (ROC) curve. The highest diagnostic accuracy of CT method and the highest diagnostic accuracy of threshold method and visual method were combined as PET-CT comprehensive diagnosis method, and the diagnostic efficiency of which was compared with the other methods. Results:Among the 226 patients with SPN, 174 cases were malignant and 52 cases were benign in pathology. ROC curve analysis showed that the area under the curve (AUC) of CT method 2 (defined Lung-RADS1.1 grade 4A and below as benign, grade 4B and above as malignant) in CT methods for qualitative diagnosis of SPN was 0.622, the sensitivity was 87.93%, and the accuracy was 76.11%, the diagnostic efficiency was higher than method 2. The AUC of the threshold method 1 (defined solid nodules that SUV max≥2.5 and ground-glass nodules that SUV max≥1.14 as malignant, the others as benign) in threshold methods for qualitative diagnosis of SPN was 0.675, the sensitivity was 85.06%, and the accuracy was 76.99%, the diagnostic efficiency was higher than other methods in the threshold methods and visual methods. The AUC of PET-CT comprehensive diagnosis method (combination of CT method 2 and threshold method 1) for qualitative diagnosis of SPN was 0.652, the sensitivity was 97.70%, and the accuracy was 82.74%, the diagnostic efficiency was higher than other methods. Conclusions:There is no significant difference among threshold method, visual method and CT method based on 18F-FDG PET-CT in qualitative diagnosis of SPN. The diagnostic efficiency of combining CT method with threshold method is significantly improved.

Deubiquitinating enzyme JOSD2 affects susceptibility of non-small cell lung carcinoma cells to anti-cancer drugs through DNA damage repair / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs.@*METHODS@#The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs.@*RESULTS@#Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05).@*CONCLUSIONS@#Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.

Quality analysis of surgical specimens of rectal cancer in the Chinese taTME registry coll-aborative database: a nationwide registered study / 中华消化外科杂志

Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.

Design of Biochemistry PBL teaching cases suitable for engineering education / 生物工程学报

Engineering education is an important part of China's higher education. With the deepening of the connotation of new engineering talents training, it is timely to carry out the curriculum reform in all directions and improve the quality of engineering talents. In order to highlight the characteristics of fostering new engineering talents, specialized courses and practical courses are becoming the focus of curriculum teaching reform. However to this end, it is urgent to explore how to strengthen fostering talents with engineering characteristics in the professional foundation courses. Taking the biochemistry course as an example, problem-based learning teaching methods were employed, appropriate teaching cases were selected, scientific and technical problems based instructional designs were explored, and students were guided to condense, analyze and solve problems. This study aims to transform the learning attitude of students from "passive" to "active", enhance students' thinking skills, highlight the engineering application of science and technology, lay the foundation for continuous and even lifelong learning, and provide a reference for fostering talents under the new engineering background.

Problems and suggestions in the implementation of integrated curriculum reform of the digestive system / 中华医学教育探索杂志

The organ-system-centered medical integrated teaching mode has become the trend of modern medical education. This model combines basic medicine with clinical medicine closely. It has been widely conducted domestically and abroad for training qualified clinicians as the main task. This paper summarized the experience of integrated curriculum reform of the digestive system in Chongqing Medical University, analyzed the performance of students involved in curriculum reform, explored the problems in the curriculum reform combined with the actual situation of Chongqing Medical University, and investigated possible solutions to accumulate the experience for further deepening the integrated curriculum reform.

Value of 18F-FDG uptake features in differential diagnosis of benign and malignant solitary pulmonary lesions / 中华核医学与分子影像杂志

Objective:To evaluate the value of 18F-FDG uptake features in differential diagnosis of benign and malignant solitary pulmonary lesions. Methods:A total of 274 patients (181 males, 93 females, age: (61.0±10.2) years) with solitary pulmonary lesions who underwent 18F-FDG PET/CT between September 2010 and March 2017 were retrospectively analyzed. The 18F-FDG uptake features of lesions were divided into 5 types: full uptake (Group A), circular uptake (Group B), multi-focus uptake (Group C), mild uptake (Group D) and no-uptake (Group E). According to the pathology or follow-up results, the incidences of benign and malignant lesions in each group were analyzed. The diagnostic efficiencies of 18F-FDG uptake feature classification(A+ B=malignancy, C+ D+ E=benign) and SUV method (lesions with SUV max≥2.5 was taken as the malignancy) were calculated. χ2 test and ROC curve were used to analyze the data. Results:The malignant incidences of Groups A-E were 86.25%(138/160), 71.05%(27/38), 31.25%(10/32), 43.48%(10/23) and 14.29%(3/21), respectively ( χ2=79.49, P<0.001), and the rate of Group A was the highest ( χ2 values: 5.11-55.84, all P<0.05). There were significant differences in the malignancy incidence between A+ B group and C+ D+ E group (83.33%(165/198) vs 30.26%(23/76)), and between SUV max≥2.5 group and SUV max<2.5 group (76.09%(175/230) vs 29.55%(13/44); χ2 values: 71.83 and 37.15, both P<0.001). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the 18F-FDG uptake feature classification and the SUV method were 87.77%(165/188) vs 93.09%(175/188), 61.63%(53/86) vs 36.05%(31/86), 79.56%(218/274) vs 75.18%(206/274), 83.33%(165/198) vs 76.09%(175/230), 69.74%(53/76) vs 70.45%(31/44), respectively. ROC curve analysis showed that the diagnostic accuracy of the 18F-FDG uptake feature classification was higher than that of SUV method (AUCs: 0.747, 0.646; Z=4.05, P<0.001). Conclusions:18F-FDG uptake feature classification can improve the diagnostic specificity and accuracy of solitary pulmonary lesions. The multi-focus uptake feature maybe a sign of benign lesions, which still needs more researches to confirm.

Effect of ergosterol peroxide derivatives on the proliferation ，migration and invasion of human triple negative breast cancer cell / 中国药房

OBJECT IVE To study the effects of ergosterol peroxide derivatives EP-3P on the proliferation ，migration and invasion of human tripe negative breast cancer cell MDA-MB- 231，and to provide reference for the development of breast cancer related drugs. METHODS MTT assay was adopted to detect the proliferation of MDA-MB- 231 cells after treated with 0（blank control），1.25，2.5，5，10，20，40 μmol/L EP-3P for 24，48 and 72 h. Wound healing assay and Transwell chamber method were adopted to detect the migration and invasion ability of MDA-MB- 231 cells after treated with 0（blank control ），5，10，20 EP-3P for 24 h. The apoptosis and cell cycle distribution were detected by flow cytometry. Western blot assay was used to detect the expressions of B-cell lympho ma-2（Bcl-2），Bcl-2 associated X protein （Bax），caspase-3，cleaved-caspase-3，cytochrome C （Cyt-C），matrix metalloproteinase- 2（MMP-2）and MMP- 9. RESULTS Compared with blank control group ，2.5，5，10，20，40 μmol/L EP-3P could significantly increase the inhibitory rate of cell proliferation （P＜0.05 or P＜0.01）in a dose and time- dependent manner. After 24 h treatment of EP- 3P（10，20 μmol/L），the rate of cell migration and the number of invasive cells were decreased significantly （P＜0.01），and cell was arrested at G 2/M stage （P＜0.05 or P＜0.01）；the apoptotic rate was increased significantly （P＜0.05）；the protein expressions of Bax ，Cyt-C and cleaved-caspase- 3 were upregulated significantly ， while those of Bcl- 2，caspase-3，MMP-2 and MMP- 9 were downregulated significantly （P＜0.01）. CONCLUSIONS EP-3P can inhibit the proliferation ，migration and invasion of human tripe negative breast cancer cells MDA-MB- 231 through mitochondrial mediated endogenous caspase pathway ，and induce the apoptosis of cells .

Analysis of the gait of stroke survivors with foot drop / 中华物理医学与康复杂志

Objective:To observe the clearance strategies of hemiplegic stroke survivors with foot drop.Methods:Thirty hemiplegic stroke survivors with foot drop formed the observation group and 30 healthy counterparts constituted the control group. A three-dimensional motion capture system was used to observe and compare the minimum toe clearance (MTC) and its variability between the two groups to draw the motion trajectory of the toe in the swing phase of their gaits. The gait parameters were correlated with the toe clearance.Results:The average MTC of the observation group subjects on both the hemiplegic and non-hemiplegic side (12.01±3.36 and 22.38±5.51mm) was significantly smaller than the control group′s averages. The variability of their MTCs on both sides was also significantly greater. Clearance on the hemiplegic side was significantly less and its variability was significantly greater. Among the observation group, MTC on the hemiplegic side was positively correlated with walking speed, step length, swing phase percentage, maximum angle of hip extension, maximum angle of knee flexion, maximum angle of ankle dorsiflexion, and the range of motion of the knee and ankle joints.Conclusions:Hemiplegic stroke survivors with foot drop walk unstably with little toe clearance. It is necessary to intervene at the hip, knee and ankle to improve their obstacle clearance.

The relationship between impaired fasting blood glucose and blood indicators based on random forest: a follow-up cohort risk prediction study / 中国实用护理杂志

Objective:To explore the relationship between blood test indicators and their changes and impaired fasting blood glucose, and to conduct risk prediction research.Methods:This study selected people who underwent a physical examination at a health management center in Jinan from 2018 to 2019, with an interval of 6 months or more between the two physical examinations, and had no history of diabetes and normal fasting blood sugar during the first year of the physical examination. We took the fasting blood glucose level in the second year as the dependent variable, and took the general examination and blood test indicators in the first year as well as the changes of these indicators as independent variables to construct the model. First, the random forest model was used to screen the independent variables, and then the logistic regression model is fitted to calculate the effect values of the independent variables.Results:A total of 4 416 subjects were enrolled in this study. After a 1-year follow-up, 3.45% (133/3 851) subjects developed prediabetic blood glucose, and 0.42% (16/3 851) developed diabetic blood glucose. The sensitivity of the model using blood test indicators to predict the risk of impaired fasting blood glucose after 1 year was 67.1%, and the specificity was 100.0%. The risk of impaired fasting blood glucose after 1 year was high in the population with older age ( OR value was 1.024, 95% CI 1.014-1.035), higher systolic blood pressure ( OR value was 1.018, 95% CI 1.011-1.025), higher body mass index ( OR value was 1.079, 95% CI 1.036-1.125), higher uric acid ( OR value was 1.003, 95% CI 1.002-1.005), higher glutamyl transpeptidase ( OR value was 1.006, 95% CI 1.003-1.010), lower creatinine ( OR value was 0.971, 95% CI 0.957-0.985), lower AST/ALT ( OR value was 0.614, 95% CI 0.411-0.917)) and lower estimated glomerular filtration rate ( OR value was 0.972, 95% CI 0.958-0.988). The sensitivity of the model using the changes of blood test indicators to predict the risk of impaired fasting blood glucose after 1 year was 65.2%, and the specificity was 99.7%. The risk of impaired fasting blood glucose is high in the population with increased triglycerides ( OR value was 1.152, 95% CI 1.057-1.257), increased alkaline phosphatase ( OR value was 1.021, 95% CI 1.012-1.030), increased albumin ( OR value was 1.087, 95% CI 1.029-1.148), increased aspartate aminotransferase ( OR value was 1.006, 95% CI 1.003-1.009), increased weight ( OR value was 1.049, 95% CI 1.019-1.081) within 1 year. Conclusions:The possibility of impaired fasting blood glucose after 1 year is high in the population with older age, higher systolic blood pressure, higher body mass index, higher uric acid, higher glutamyl transpeptidase, lower creatinine, lower AST/ALT and lower estimated glomerular filtration rate. The possibility of impaired fasting blood glucose is high in the population with increased triglycerides, increased alkaline phosphatase, increased albumin, increased aspartate aminotransferase and increased weight with in 1 year. When the above situation occurs in the physical examination, the blood glucose should be monitored and timely intervention should be taken to prevent the development of diabetes.

Effect of licochalcone A on osteoarthritis in rats and its relationship with p38-MAPK inflammatory signaling pathway / 中国基层医药

Objective:To investigate the effect of licochalcone A on osteoarthritis in rats and its relationship with p38-MAPK inflammatory signaling pathway.Methods:A total of 160 male Wistar rats were randomly divided into blank non-intervention, blank intervention, arthritis non- intervention and arthritis intervention groups with 40 rats in each group. Rats in the arthritis groups were subjected to unilateral anterior cruciate ligament transection, while rats in the blank groups were only subjected to skin incision and suture. Rats in the intervention groups were treated by intra-articular injection of 1 mL 10 μmol/L licochalcone A for 8 successive weeks. Eight weeks later, the cartilage of rats in each group was stained with safranin, and osteoarthritis soft tissue was scored according to Osteoarthritis Research Society International guideline under the optical microscope. The cartilage was cultured in low glucose cell culture medium supplemented with 5% fetal bovine serum for 48 hours. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan and collagen II in the medium were determined by the chemiluminescence reaction method. The expression levels of p38, phosphorylated p38 (p-p38) and matrix metalloproteinase in cartilage tissue were detected by western blot assay. Results:The progress of osteoarthritis in rats treated with licochalcone A was slow. The Osteoarthritis Research Society International score in the arthritis intervention group was significantly lower than that in the arthritis non-intervention group [(3.8 ± 1.7) points vs. (9.7 ± 1.2) points, P = 0.0064]. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan, and collagen II in the arthritis intervention group were (77.84 ± 17.65) μmol/mg and (6.78 ± 1.76) ng/mg, (89.78 ± 9.76) μg/mg, and (1.78 ± 0.76) μg/mg, respectively, which were significantly lower than those in the arthritis non-intervention group [(107.56 ± 18.74) μmol/mg, (10.756 ± 1.87) ng/mg, (125.75 ± 8.87) μg/mg, (3.76 ± 0.88) μg/mg, (NO: P = 0.002; PGE 2: P < 0.001; sGAG: P < 0.001; Collagen II: P < 0.001). Western blot assay results revealed that the relative expression of p38, p-p38, p-p38 to total p38 ratio, matrix metalloproteinase in the arthritis intervention group were (3 454 ± 421), (2 072 ± 175), (0.65 ± 0.14 )and (1 776 ± 765), respectively, which were significantly lower than those in the arthritis non-intervention group (5 322 ± 323), (4 257 ± 184), (0.89 ± 0.11), (3 865 ± 874)( p38: P < 0.001; p-p38: P < 0.001; p-p38/p38: P = 0.002; MMP: P = 0.001). Conclusion:Licochalcone A can delay the progression of osteoarthritis in rats with osteoarthritis through inhibiting inflammatory reaction and cartilage matrix degradation, and p38-MAPK signaling pathway may be involved in the regulation process.

The Role of miR-34c-5p in Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Background and Objectives@#Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs. @*Methods@#and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN. @*Conclusions@#miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.

The Role of miR-34c-5p in Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Background and Objectives@#Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs. @*Methods@#and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN. @*Conclusions@#miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.

Daratumumab for the treatment of primary systemic amyloidosis: a multicenter retrospective analysis / 中华内科杂志

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.