Expression of STEAP1 in bladder transitional cell carcinoma and its potential diagnostic value / 国际检验医学杂志

Objective To investigate the expression and potential diagnostic value of six-transmembrane epithelial antigen of prostate 1(STEAP1)in bladder transitional cell carcinoma.Methods 52 patients with transitional cell carcinoma of the bladder who underwent surgical treatment at the 940th Hospital of Joint Lo-gistics Support Force of the Chinese People's Liberation Army from June 2021 to December 2022 were select-ed as the observation group.In addition,52 patients with benign tumors of the bladder who matched basic clin-ical data such as age,gender,and disease incidence were selected as the control group.The relative expression levels of STEAP1 and STEAP1 mRNA in bladder tumor tissues of patients in the two groups were deter-mined by enzyme-linked immunosorbent assay and real-time fluorescence quantitative PCR,and the relative expression levels of STEAP1 and STEAP1 mRNA in bladder tumor tissues of patients with different patho-logical parameters were compared.Spearman correlation analysis and binary Logistic regression analysis were used to screen the risk factors for the occurrence and clinical stage of bladder transitional cell carcinoma.Re-ceiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the diagnos-tic and predictive value of each indicator for bladder transitional cell carcinoma.Results The relative expres-sion levels of STEAP1 and STEAP1 mRNA in bladder tumor tissues in observation group were significantly higher than those in control group,with statistical significance(P＜0.05).The relative expression levels of STEAP1 and STEAP1 mRNA in bladder tumor tissues of patients with middle and advanced bladder transi-tional cell carcinoma were significantly higher than those of patients with early bladder transitional cell carci-noma,with statistical significance(P＜0.05).Binary Logistic regression analysis showed that the relative ex-pression level of STEAP1 and STEAP1 mRNA in bladder tumor tissues of patients were independent risk fac-tors for the development of bladder transitional cell carcinoma and middle and advanced bladder transitional cell carcinoma(P＜0.05).ROC curve analysis showed that the AUC of STEAP1 and STEAP1 mRNA inde-pendently predicting the occurrence of bladder transitional cell carcinoma was 0.841(95％CI:0.760-0.922,P＜0.001)and 0.936(95％CI:0.893-0.980,P＜0.001),respectively,both of which had high predictive ef-ficacy.Conclusion The relative expression levels of STEAP1 and STEAP1 mRNA in bladder tumor tissues of patients are positively correlated with the occurrence of bladder transitional cell carcinoma and the middle and advanced bladder transitional cell carcinoma,suggesting that STEAP1 can be used as a potential marker for di-agnosis and prediction of the occurrence and development of bladder transitional cell carcinoma.

The mechanism of extract of ginkgo biloba inducing mitochondrial autophagy in breast cancer cells MCF-7 / 国际肿瘤学杂志

Objective:To investigate the mechanism of extract of ginkgo biloba (EGB) on mitochondrial autophagy in breast cancer cells MCF-7.Methods:Breast cancer MCF-7 cells were divided into four groups. EGB with mass concentrations of 40, 80, 120 mg/L was used to incubate breast cancer MCF-7 cells for 24 h or 48 h, as a low concentration group of EGB, a medium concentration group of EGB, and a high concentration group of EGB. Breast cancer MCF-7 cells without intervention were taken as control group. Cell proliferation was measured using MTT assay; Flow cytometry was used to detect cell apoptosis; Immunofluorescence assay was used to determine the contents of prostacyclin (P62), microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and caspase-3; The levels of multidrug resistance-associated protein 1 (MRP1), multidrug resistance gene 1 (MDR1) and breast cancer resistance protein (BCRP) were identified by PCR; Western blotting was used to detect the expression of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), p-ERK, and p-MAPK proteins in cells.Results:The results of MTT assay for cell proliferation showed that cell proliferation at 24 h in control group, EGB low, medium and high concentration groups were 0.95±0.14, 0.65±0.09, 0.51±0.07, 0.37±0.04, respectively, with a statistically significant difference ( F=43.13, P<0.001), cell proliferation at 48 h were 1.32±0.19, 0.54±0.08, 0.32±0.05, 0.15±0.02, respectively, with a statistically significant difference ( F=141.30, P<0.001). Compared with 24 h, cell proliferation was decreased in EGB low, medium and high concentration groups at 48 h (all P<0.05). Pairwise comparison showed that EGB treatment significantly decreased MCF-7 cell viability and cell proliferation was decreased in turn at 24 and 48 h in control group, low, medium, high EGB groups (all P<0.05). Flow cytometry analysis revealed that the apoptosis rates of MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.12%±0.23%, 9.28%±0.45%, 15.17%±1.28% and 22.21%±2.32%, respectively, with a statistically significant difference ( F=128.80, P<0.001). Pairwise comparison showed that the apoptosis rate of control group, EGB low, medium and high concentration groups were increased in turn (all P<0.05). The results of immunofluorescence assay showed that the protein relative expression levels of P62 protein in MCF-7 cells of control group, EGB low, medium and high concentration groups were 3.34±0.52, 2.85±0.47, 2.02±0.18 and 1.08±0.21, respectively, with a statistically significant difference ( F=41.55, P<0.001). LC3Ⅱ protein relative expression levels were 0.24±0.05, 1.02±0.14, 1.47±0.26, 1.95±0.21, respectively, with a statistically significant difference ( F=94.82, P<0.001). The relative expression levels of caspase-3 protein were 0.25±0.03, 0.68±0.21, 1.12±0.17 and 1.65±0.23, respectively, with a statistically significant difference ( F=68.09, P<0.001). Pairwise comparison showed that LC3Ⅱ and caspase-3 protein expression levels were increased in turn in control group, EGB low, medium and high concentration groups, while P62 protein expression levels were decreased in turn (all P<0.05). The PCR experiment results showed that the MRP1 mRNA level of MCF-7 cells in control group, EGB low, medium and high concentration groups were 1.06±0.14, 0.83±0.18, 0.71±0.11, 0.52±0.08, respectively, with a statistically significant difference ( F=17.41, P<0.001). The mRNA levels of MDR1 were 1.14±0.17, 0.75±0.13, 0.60±0.09, 0.48±0.06, respectively, with a statistically significant difference ( F=34.40, P<0.001). BCRP mRNA levels were 1.09±0.11, 0.88±0.13, 0.69±0.07, 0.57±0.05, respectively, with a statistically significant difference ( F=34.13, P<0.001). Pairwise comparison showed that the levels of MRP1, MDR1 and BCRP mRNA were decreased in turn in control group, EGB low, medium and high concentration groups (all P<0.05). The results of Western blotting showed that the expression of ERK in MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.54±0.38, 1.89±0.25, 1.55±0.21, 1.12±0.16, respectively, with a statistically significant difference ( F=31.18, P<0.001). MAPK expression were 2.47±0.34, 1.96±0.29, 1.63±0.27, 1.20±0.24, respectively, with a statistically significant difference ( F=20.90, P<0.001). p-ERK expression were 2.03±0.29, 1.74±0.21, 1.45±0.11, 1.18±0.24, respectively, with a statistically significant difference ( F=16.31, P<0.001). p-MAPK expression were 2.26±0.47, 1.90±0.41, 1.61±0.33, 1.35±0.16, respectively, with a statistically significant difference ( F=7.01, P=0.002). Pairwise comparison showed that the expressions of ERK, MAPK, p-ERK and p-MAPK in control group, EGB low, medium and high concentration groups were decreased in turn (all P<0.05) . Conclusion:EGB can inhibit the proliferation of breast cancer MCF-7 cells, promote the apoptosis of MCF-7 cells, decrease the expression of P62 protein, increase the expression of LC3Ⅱ and caspase-3 protein, induce mitochondrial autophagy.

Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study / 中华消化外科杂志

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

The application research of analogical thinking combined with situational teaching method to create a happy learning situation in ophthalmic nursing teaching / 中华医学教育探索杂志

Objective:To explore the application of analogical thinking combined with situational teaching method to create a happy learning situation in ophthalmic nursing practice teaching.Methods:A total of 90 nursing students who had practice in Department of Ophthalmology, Xijing Hospital, Air Force Medical University, from October 2020 to January 2022 were selected as the research objects. According to different teaching methods, they were divided into control group and observation group. The control group ( n=45) adopted conventional teaching, while the observation group ( n=45) adopted analogical thinking combined with situational teaching method. The two groups of nursing students were evaluated by comprehensive examination results, teaching effect questionnaire and students' overall satisfaction with their teachers. SPSS 22.0 was used for t-test and Chi-square test. Results:The test scores of theoretical knowledge [(85.39±1.57) vs. (84.41±1.34)] and nursing skills [(87.52±0.04) vs. (82.64±0.05)] of observation group were both higher than those of control group. In the observation group, the students' awareness of medication safety, professional interest and independent learning, cooperation and organization ability, independent thinking and independent learning ability, the purpose of multi-disciplinary knowledge integration, information and knowledge range improvement, clinical thinking communication ability enhancement, flexible application of theoretical knowledge, practical operation ability enhancement, and the cultivation of innovation consciousness were all improved. And all the scores were better than those of the control group. The satisfaction of teachers in the observation group on students' learning attitude, language expression, calling communication ability and independent problem-solving ability was higher than that in the control group ( P < 0.05). Conclusion:The combination of analogical thinking and the situational teaching method to create a happy learning situation can improve the average scores of nursing students and nursing skills, and significantly improve the satisfaction of students to the teachers.

Clinical characteristics and meteorological factors of patients with chronic heart failure in Qinghai plateau area / 公共卫生与预防医学

Objective To analyze the clinical characteristics and meteorological factors of patients with chronic heart failure (CHF) in Qinghai Plateau area, and to provide a theoretical basis for the diagnosis and treatment of patients with chronic heart failure. Methods A total of 356 patients with CHF admitted to our hospital in Qinghai Plateau area from 2019 to 2020 were selected, and the number of cases, age, gender, comorbidity, NYHA cardiac function classification of CHF patients in Qinghai Plateau area from 2019 to 2020 were counted. To compare NYHA cardiac function classification and underlying diseases in CHF patients at different ages and altitudes in Qinghai Plateau area. The daily average temperature (℃), daily temperature and daily range (℃), daily average wind speed (m/s), daily average air pressure (kPa) and daily average relative humidity (%) in Qinghai Plateau from 2019 to 2020 were collected. According to the general clinical data of patients, the changes of the monthly incidence of CHF patients were analyzed. Pearson correlation analysis was used to compare the correlation between the monthly incidence of CHF patients and meteorological factors, and to explore the influence of meteorological factors on the incidence of CHD in Qinghai Plateau. Results Among the 356 CHF patients, there were 181 males and 175 females, with an average age of (72.47 ±6.49) years old. The NYHA classification of cardiac function was grade II in 103 cases, grade ⅲ in 198 cases, and grade ⅳ in 55 cases. NYHA cardiac function classification increased with age, and there was significant difference in NYHA cardiac function classification among CHF patients of different ages (P<0.05). Among 356 CHF patients, 91 cases (25.56%) were complicated with hypertension, 63 cases (17.70%) were complicated with coronary heart disease, 57 cases (16.01%) were complicated with diabetes, and 40 cases (11.24%) were complicated with hypergenic heart disease. 25 cases (7.02%) were complicated with heart valve disease. Hypertension, coronary heart disease, diabetes mellitus, hypergenic heart disease and valvular heart disease increased with age, and there were statistically significant differences between CHF patients with different ages and underlying diseases (P<0.05). CHF patients in Qinghai Plateau region were mainly concentrated in January-March and October-December. Taking the number of CHD admissions as the dependent variable and each meteorological factor as the independent variable, the correlation between each factor was compared. The results showed that the number of CHF cases was positively correlated with the daily temperature range and daily mean air pressure, and negatively correlated with the average daily temperature (P<0.05). Daily temperature range (OR=2.61) and daily mean air pressure (OR=1.89) were independent risk factors for CHF in Qinghai Plateau area (P<0.05). Conclusion CHF is more prevalent in elderly people in high altitude areas in Qinghai Plateau. For months with high temperature changes, wind speed, we should pay attention to weather changes and take preventive measures in advance.

Effects of sewage treatment plant sludge and microplasticexposure on oxidative stress levels in zebrafish / 预防医学

Objective @#To investigate the effects of the exposure of sludge from sewage treatment plants and microplastic extracted from sludge on the oxidative stress levels in zebrafish, so as to put insights into the research into the impact of sludge and microplastics on human health. @*Methods @#Adult wild AB zebrafish were exposed to five groups of sludge (0, 12.5, 25, 50 and 75 g/L) and four groups of microplastics extract from sludge (0, 240, 480, 960/L), with 24 zebrafish in each group. The color, activity and death of zebrafish were observed every day. The contents of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) were detected 0 h, 24 h, 48 h, 72 h, 96 h and 7 d post-exposure. A two-factor ANOVA was used to analyze the effects of different concentrations and time of exposure on the indicators above. @*Results @#Under 75 g/L sludge exposure, zebrafish began to show mortality at 72 h and all died after 7 d. The zebrafish in the other sludge groups and all microplastic groups had normal color and activity, and no mortality was observed. Sludge concentration interacted with exposure time to affect SOD, CAT, GSH and MDA (P<0.05). With increasing sludge concentration and exposure time, SOD decreased, MDA increased, CAT increased first and then decreased, GSH decreased first and then increased, and GSH continued to decrease since 24 h in the 75 g/L group. The microplastic concentration interacted with exposure time to affect SOD and GSH (P<0.05), but not CAT or MDA (P>0.05). With increasing microplastic concentration and exposure time, SOD and MDA increased, CAT increased first and then decreased, the GSH was slightly increased at 24 h and decreased after 72 h.@*Conclusion @#Both sludge and microplastics extracted from sludge can induce oxidative stress damage in zebrafish, and exposure time and concentration can interact to affect oxidative stress levels. The microplastics extracted from sludge have less effect on oxidative stress levels in zebrafish than sludge.

HPLC Fingerprint Analysis of Benchmark Sample of Yanghetang / 中国实验方剂学杂志

ObjectiveTo establish a high performance liquid chromatography（HPLC） fingerprint of Yanghetang benchmark sample， and evaluate its quality with chemometric methods， so as to provide a reference for the quality control of this benchmark sample. MethodHPLC was used to establish the fingerprint of Yanghetang benchmark sample with ZORBAX SB-C18 column（4.6 mm×250 mm， 5 μm）， the mobile phase was consisted of acetonitrile（A） -0.05% phosphoric acid aqueous solution （containing 0.05% triethylamine solution）（B） for gradient elution（0-5 min， 2%-3%A； 5-15 min， 3%-5%A； 15-65 min， 5%-30%A； 65-90 min， 30%-70%A）， the flow rate was 1.0 mL·min-1， the column temperature was 35 ℃， and the detection wavelength was 210， 260 nm. Traditional Chinese Medicine（TCM） Chromatographic Fingerprint Similarity Evaluation System （2012 edition） combined with cluster analysis， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to evaluate the quality differences between different batches of Yanghetang benchmark samples， and to find the main chemical components responsible for the quality differences. ResultHPLC fingerprint of Yanghetang benchmark sample was established， 13 common peaks were identified and attributed to each common peak， including peaks 2 and 8 from Rehmanniae Radix Praeparata， peaks 10 and 11 from Cinnamomi Cortex， peaks 1， 3-6 from fried Sinapis Semen， peak 13 from Ephedrae Herba， and peaks 7， 9， 12 from Glycyrrhizae Radix et Rhizoma. Eight of them were identified by comparing with control substance， which were 5-hydroxymethylfurfural（peak 2）， sinapine thiocyanate（peak 4）， glycyrrhizin（peak 7）， verbascoside（peak 8）， cinnamic acid（peak 10）， cinnamaldehyde（peak 11）， glycyrrhizic acid（peak 12） and ephedrine hydrochloride（peak 13）. The similarities of the HPLC fingerprints of 15 batches of Yanghetang benchmark samples with the control fingerprint were all greater than 0.80. The three chemometric methods could classify the samples into two categories. Eight differential components were screened out， among which 5-hydroxymethylfurfural， sinapine thiocyanate， verbascoside and ephedrine hydrochloride were identified. ConclusionThe established fingerprint analysis method is accurate， stable and reproducible， which basically reflects the overall chemical composition of Yanghetang benchmark sample， and can provide a basis for establishment of quality standards for compound preparations of this famous classical formula.

Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease / 中华心血管病杂志

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin / 药物分析学报

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Treatment of degenerative lumbar lateral recess stenosis with full endoscopic lamina fenestration discectomy / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of full endoscopic lamina fenestration discectomy (Endo-LOVE) with full endoscopic transforaminal approach discectomy in the treatment of degenerative lumbar lateral recess stenosis.@*METHODS@#A retrospective analysis of 48 patients with degenerative lumbar lateral recess stenosis between March 2018 and March 2019 was performed. There were 32 males and 16 females, aged from 60 to 83 years old with an average of (72.9±6.5) years, course of disease ranged from 5 to 16 years with an average of (8.0±2.8) years. The patients were divided into observation group and control group according to surgical approaches. There were 28 cases in observation group, underwent Endo-LOVE surgery;and 20 cases in control group, underwent full endoscopic foraminal approach discectomy. The operation time, intraoperative blood loss, hospitalization day and complications were observed between two groups. Visual analgue scale (VAS), Japanese Orthopaedic Association(JOA), Oswestry Disability Index(ODI), lateral crypt angle were compared between two groups. And clinical effects were evaluated by modified Macnab standard.@*RESULTS@#There was no significant difference in follow-up and operation time between two groups (P>0.05). Intraoperative blood loss was from 5 to 15 ml with an average of (8.4±3.6) ml in observation group and 5 to 25 ml with an average of (11.5±5.4) ml in control group. The hospitalization day was from 5 to 8 days with an average of (6.0±1.0) days in observation group and 6 to 9 days with an average (7.2±1.1) days in control group. Intraoperative blood loss and hospitalization day were significantly lower in observation group(P<0.05). There were no serious complications in both groups. The VAS, JOA scores, and ODI at 3-month and final follow-up were significantly improved in both groups (P<0.05), and observation group was significantly better than control group (P<0.05). The skeletal lateral crypt angle and soft lateral crypt angle were significantly greater than the preoperative angle at 3 days postoperatively(P<0.05), and observation group was significantly better than control group(P<0.05). At the final follow-up, the modified Macnab criteria was used to assess clinical efficacy, in observation group, 22 patients obtained excellent results, 5 good and 1 fair;while 11 excellent, 4 good and 5 fair in control group;the clinical efficacy of observation group was significantly better than that of control group(P<0.05).@*CONCLUSION@#Both surgical methods are performed under direct vision, with high safety and good clinical efficacy. However, Endo-LOVE enlarged the lateral crypt more fully.

Construction and Application of Rib Fracture Diagnosis Model Based on YOLOv3 Algorithm / 法医学杂志

OBJECTIVES@#The artificial intelligence-aided diagnosis model of rib fractures based on YOLOv3 algorithm was established and applied to practical case to explore the application advantages in rib fracture cases in forensic medicine.@*METHODS@#DICOM format CT images of 884 cases with rib fractures caused by thoracic trauma were collected, and 801 of them were used as training and validation sets. A rib fracture diagnosis model based on YOLOv3 algorithm and Darknet53 as the backbone network was built. After the model was established, 83 cases were taken as the test set, and the precision rate, recall rate, F1-score and radiology interpretation time were calculated. The model was used to diagnose a practical case and compared with manual diagnosis.@*RESULTS@#The established model was used to test 83 cases, the fracture precision rate of this model was 90.5%, the recall rate was 75.4%, F1-score was 0.82, the radiology interpretation time was 4.4 images per second and the identification time of each patient's data was 21 s, much faster than manual diagnosis. The recognition results of the model was consistent with that of the manual diagnosis.@*CONCLUSIONS@#The rib fracture diagnosis model in practical case based on YOLOv3 algorithm can quickly and accurately identify fractures, and the model is easy to operate. It can be used as an auxiliary diagnostic technique in forensic clinical identification.

Progress of Research on Novel Immune Checkpoints in Occurrence,Development and Immunotherapy of Gastric Cancer / 胃肠病学

Gastric cancer is one of the most common cancers in the world,and with the rise of immune-targeted therapy,it has provided new treatment options for many patients with advanced gastric cancer.However,not all cancer patients can benefit from monoclonal antibody therapy against programmed death-1 and its ligand and against cytotoxic T lymphocyte associated antigen-4.Therefore,the discovery of new immune checkpoints has become a future therapeutic trend.In this review,we summarized and analyzed the biological characteristics of V-domain Ig suppressor of T cell activation,B7 homolog 3 and lymphocyte-activation gene 3 of novel immune checkpoint T cell activation,as well as their effects on the occurrence and development of gastric cancer.At the same time,the effectiveness of corresponding immunosuppressants in preclinical and clinical trials was also evaluated,in order to provide a theoretical reference for the targeted therapy of gastric cancer.

Clinical analysis of patients with oral and maxillofacial infections in oral emergency / 北京大学学报(医学版)

OBJECTIVE@#To analyze the composition, incidence and clinical characteristics of oral and maxillofacial infections in oral emergency.@*METHODS@#A retrospective study on patients with oral and maxillofacial infections who visited the Department of Oral Emergency in Peking University School and Hospital of Stomatology from January 2017 to December 2019 was conducted. General characteristics, such as disease composition, gender, age distribution and position of involved teeth were analyzed.@*RESULTS@#A total of 8 277 patients with oral and maxillofacial infections were finally collected, including 4 378 male patients (52.9%) and 3 899 female patients (47.1%), with gender ratio of 1.12:1. The common diseases were periodontal abscess (3 826 cases, 46.2%), alveolar abscess (3 537 cases, 42.7%), maxillofacial space infection (740 cases, 9.0%), sialadenitis (108 cases, 1.3%), furuncle & carbuncle (56 cases, 0.7%) and osteomyelitis (10 cases, 0.1%). Male patients were more easily affected by periodontal abscess, space infection and furuncle & carbuncle than female patients with the gender ratios 1.24:1, 1.26:1, 2.50:1 individually, while the incidence of alveolar abscess, sialadenitis, furuncle & carbuncle had no significant gender difference. Different diseases were prone to occur at different ages. The peak ages of alveolar abscess were 5-9 and 27-67 years, while the peak age of periodontal abscess was 30-64 years. Space infection tended to occur between 21-67 years. There were 7 363 patients with oral abscess (3 826 patients with periodontal abscess and 3 537 patients with alveolar abscess), accounting for 88.9% of all the patients with oral and maxillofacial infections, involving 7 999 teeth, including 717 deciduous teeth and 7 282 permanent teeth. Periodontal abscess usually occurred in permanent teeth, especially the molar teeth. Alveolar abscess may occur in both primary teeth and permanent teeth. In primary teeth, the most vulnerable sites were primary molar teeth and maxillary central incisors while in permanent teeth the most vulnerable sites were first molar teeth.@*CONCLUSION@#Understanding the incidence of oral and maxillofacial infection was conducive to the correct diagnosis and effective treatment of clinical diseases, as well as targeted education for patients of different ages and genders to prevent the occurrence of diseases.

Excimer laser coronary angioplasty combined with thrombus aspiration catheter successfully treated 3 patients of acute myocardial infarction with massive thrombus in right coronary artery / 中国介入心脏病学杂志

For patients with severe coronary thrombosis burden,when conventional methods still cannot restore ideal blood flow,excimer laser coronary angioplasty(ELCA)can be used as an important auxiliary method for percutaneous coronary intervention(PCI).It can reduce the occurrence of slow blood flow or no-reflow,increase coronary blood flow,improve myocardial perfusion,and achieve higher immediate and clinical success rates.This article introduced the diagnosis and treatment of 3 patients with massive right coronary artery thrombosis treated with ELCA combined with thrombus aspiration.All 3 patients successfully opened blood vessels,significantly reduced the thrombus load,and achieved good immediate and clinical effects.No complications such as vascular perforation and cardiac tamponade occurred during the treatment.

Analysis of common protocol deviations in drug clinical trials of rheumatism / 中华风湿病学杂志

Objective:The common protocol deviation (PD) in clinical trials of drugs for rheumatic diseases were analyzed to provide reference for improving the quality of clinical trials and protecting the safety and rights of subjects.Methods:Protocol deviation (PD) reports of completed projects conducted by Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University, from 2017 to 2021 were collected and sorted out for analysis. Results:The common PD and proportion of deviation were deviation from protocol study procedures (25.4%, 44/173), low medication compliance (23.7%, 41/173), visits out of the scheduled visit dates or the tests or examinations out od the inspection window period (19.1%, 33/173), missed visit or missed laboratory tests (17.9%, 31/174), using of prohibited drugs (9.2%, 16/173) and violation of inclusion criteria or exclusion criteria (4.6%, 8/173). 135 cases were mild and 38 cases severe deviation. PPS was eliminated in 5 subjects during statistical analysis.Conclusion:①Investigator training should be strengthened and the operability should be taken into account in clinical trial design. In the implementation process, the inclusion and exclusion criteria should be strictly followed and the should adherent to study procedures. ②The institution should actively promote the development of hospital information system to reduce investigator associated PD. ③The education and management of subject should be strengthened to ensure their compliance and improve the quality of clinical trials to protect the safety and rights of subjects. ④Institute should strengthen the management of trail supervisors and emphasis on problems identification during inspections.

Short-term and long-term prognosis analysis of anatomical liver resection for the treatment of perihilar cholangiocarcinoma / 肿瘤

Objective:To explore the short-term and long-term prognostic outcomes of anatomical liver resection(AR)for patients with perihilar cholangio-carcinoma. Methods:This is a retrospective study.All data were obtained from 4 centers,including The First Affiliated Hospital of Army Medical University,Eastern Hepatobiliary Hospital of Naval Medical University,Sichuan Provincial People's Hospital and Affiliated Hospital of Qinghai University,of a multi-center database.A total of 305 consecutive perihilar cholangiocarcinoma patients receiving radical resection between January 2013 and June 2021 were included in this study.According to the method of liver resection,all patients were divided into the AR group(n=205)and the non-anatomical liver resection(NAR)group(n=100).The baseline characteristics,short-term prognosis and long-term prognosis of the 2 groups were compared. Results:The perioperative transfusion rate and the 30-day complication rate were significantly lower in the AR group than those in the NAR group(P＜0.05).There was no statistically significant difference in the survival rates between the AR and the NAR groups(P＞0.05). Conclusion:The 2 hepatic resection modalities had no obvious effect on the long-term prognosis of perihilar cholangiocarcinoma patients after radical resection,but choosing AR tends to achieve a better short-term prognosis and is worth promoting in clinical practice.

Theoretical analysis and practical applications of the catalytic mechanism of flavonoid 6-hydroxylase / 生物工程学报

Insufficient catalytic efficiency of flavonoid 6-hydroxylases in the fermentative production of scutellarin leads to the formation of at least about 18% of by-products. Here, the catalytic mechanisms of two flavonoid 6-hydroxylases, CYP82D4 and CYP706X, were investigated by molecular dynamics simulations and quantum chemical calculations. Our results show that CYP82D4 and CYP706X have almost identical energy barriers at the rate-determining step and thus similar reaction rates, while the relatively low substrate binding energy of CYP82D4 may facilitate product release, which is directly responsible for its higher catalytic efficiency. Based on the study of substrate entry and release processes, the catalytic efficiency of the L540A mutation of CYP82D4 increased by 1.37-fold, demonstrating the feasibility of theoretical calculations-guided engineering of flavonoid 6-hydroxylase. Overall, this study reveals the catalytic mechanism of flavonoid 6-hydroxylases, which may facilitate the modification and optimization of flavonoid 6-hydroxylases for efficient fermentative production of scutellarin.

Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method / 中国中药杂志

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ / 临床肝胆病杂志

Objective To investigate the differences in UGT1A1 gene mutation sites, haplotypes, and diplotypes between patients with Gilbert syndrome (GS) and those with Crigler-Najjar syndrome type Ⅱ (CN-2). Methods A retrospective analysis was performed for the clinical data of 138 patients with GS or CN-2 who attended Beijing YouAn Hospital, Capital Medical University, from January 1, 2010 to December 31, 2019, with 109 patients in the GS group and 29 patients in the CN-2 group, and the differences in mutation sites were analyzed between the two phenotypes. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. SNPStats software was used to perform linkage disequilibrium (LD) and haplotype analyses of mutation sites. Strong LD was defined as both | D ′| and r 2 > 0.8, and moderate LD was defined as | D ′| > 0.8 and r 2 > 0.4. Results UGT1A1 gene detection was performed for all patients, and mutations mainly included -3279T > G mutation (104 patients, 75.36%) and -3152G > A mutation (82 patients, 59.42%) in the upstream promoter PBREM region, a promoter TATA box TA insertion mutation (88 patients, 63.77%), and c.211G > A mutation in Exon 1 of the coding region (66 patients, 47.83%). Compared with the CN-2 group, the GS group had a significantly higher proportion of PBREM region -3279T > G mutation (82.57% vs 48.28%, χ 2 =14.508, P A mutation (68.81% vs 24.14%, χ 2 =18.955, P (TA) 7 mutation (72.48% vs 31.03%, χ 2 =17.027, P 0.8, r 2 > 0.8) between (TA) 6 > (TA) 7 and -3152G > A and moderate LD (| D ′| > 0.8, r 2 > 0.4) between (TA) 6 > (TA) 7 and -3279T > G, between -3152G > A and -3279T > G, between (TA) 6 > (TA) 7 and c.211G > A, and between -3279T > G and c.211G > A. Haplotype frequency analysis showed that compared with the CN-2 group, the GS group had a significantly higher frequency of haplotype -3279G—-3152A—(TA) 7 (45.72% vs 17.24%, χ 2 =7.833, P =0.005) and significantly lower frequencies of c.1456G (4.10% vs 16.48%, χ 2 =4.873, P =0.027) and c.211A—c.1456G (1.86% vs 24.90%, χ 2 =15.210, P < 0.001). The diplotype analysis showed that diplotypes consisting of haplotype c.1456G or c.211A—c.1456G were associated with a higher level of total bilirubin (TBil). Conclusion There are differences in common mutation sites and major haplotypes of the UGT1A1 gene between patients with GS and those with CN-2, and the common diplotypes of CN-2 correspond to a higher level of TBil.