Mechanism on Banxia Xiexintang Inducing Ferroptosis in Gastric Cancer Cells Based on Nrf2/GPX4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang （BXT） on the proliferation of human gastric cancer HGC-27， MKN-45， and AGS cells and its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the effects of different concentrations of BXT-containing serum （5%， 10%， and 20%） on the proliferation of HGC-27， MKN-45， and AGS cells. A mitochondrial membrane potential probe （TMRE） was used to detect the expression of mitochondrial membrane potential in cells. A kit was used to detect iron ion （Fe2+） content， lipid peroxide （LPO）， and superoxide dismutase （SOD） activity. Western blot was used to detect the protein expression levels of glycogen synthase3β （GSK3β）， phosphorylated GSK3β （p-GSK3β）， nuclear factor E2 related factor 2 （Nrf2）， and glutathione peroxidase 4 （GPX4）. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of member 11 of the cystine/glutamic acid reverse transporter solute vector family 7 （SLC7A11）， member 2 of the heavy chain solute vector family 3 （SLC3A2）， transferrin receptor 3 （TFRC）， and tumor protein （TP）53. ResultCCK-8 results showed that BXT and capecitabine could significantly reduce the survival rate of three kinds of gastric cancer cells after treatment with drug-containing serum for 24 h （P<0.01）. After 48 h of intervention with drug-containing serum， the survival rate of three kinds of gastric cancer cells was significantly decreased in both the capecitabine group and the BXT group compared with the blank group. The BXT group was dose-dependent， with 20% BXT having the most significant effect （P<0.01）. In terms of biochemical indicators of ferroptosis， compared with the blank group， BXT and capecitabine significantly decreased the expression of mitochondrial membrane potential （P<0.01） and SOD activity （P<0.01） and significantly increased the contents of LPO and Fe2+ （P<0.01）， so as to improve the sensitivity of gastric cancer cells to ferroptosis. In terms of the Nrf2/GPX4 pathway， compared with the blank group， the BXT group could reduce the protein expressions of p-GSK3β， Nrf2， and GPX4 （P<0.01） in gastric cancer cells and increase mRNA expressions of SLC7A11 and SLC3A2 （P<0.05）. It could also increase the protein expression of GSK3β （P<0.01） and mRNA expression of TP53 and TFRC （P<0.05， P<0.01） in gastric cancer cells. Inhibition of the Nrf2/GPX4 pathway induces ferroptosis in gastric cancer cells. Compared with the capecitabine group， the 20% BXT group showed a more obvious effect. ConclusionBanxia Xiexintang can induce ferroptosis in gastric cancer cells HGC-27， MKN-45， and AGS by inhibiting the Nrf2/GPX4 pathway.

Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion / 中华病理学杂志

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

Effects of methimazole on urinary metabolomics in hyperthyroidism rats / 中国药房

OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats， and to preliminarily investigate its possible mechanism. METHODS Thirty SD rats were randomly divided into control group， model group and methimazole group， with 10 rats in each group. Except for the control group， the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days； at the same time， methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day. The basic condition of the rats was observed， and the body weight and anal temperature were measured. After the last medication， the serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， free tetraiodothyronine （FT4）， and thyroid stimulating hormone （TSH） were determined； 24-hour urine was collected on the 15th day after administration. UPLC-TOF-MS was used to analyze the urine metabolomics of rats. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites， and potential metabolic pathways were analyzed by using HMDB and KEGG. RESULTS Compared with the control group， the rectal temperature， serum levels of T3， T4， FT3 and FT4， the expressions of differential metabolites sebacic acid， cholic acid 3-O-glucuronic acid and N6， N6， N6-trimethyl-L-lysine in urine were significantly up-regulated， while body weight， serum level of TSH， the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated （P＜0.01）. Compared with model group， above indexes of rats were reversed significantly in methimazole group （P＜0.01 or P＜0.05）. Above five differential metabolites were mainly involved in four signaling pathways: pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism. CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism.

A Precise and Portable Detection System for Infectious Pathogens Based on CRISPR/Cas Technology / 分析化学

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

A Bibliometric and Visual Analysis of the Current Status and Trends of Foren-sic Mixed Stain Research / 法医学杂志

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Effect of manually reverse mixing times on erythrocyte sedimentation rate / 国际检验医学杂志

Objective To investigate the effect of manually reverse mixing times on erythrocyte sedimenta-tion rate(ESR).Methods The ESR samples of 200 subjects were manually mixed for 3,6,9,12 and 15 times before detection.The ESR results of each group were collected,and the samples were manually mixed for 12 times as the reference standard.R(4.2.1)software was used for data analysis,Shapiro-Wilk was used for normal distribution test,Friedman test was used for multi-group comparison,and Spearman correlation analy-sis was used to analyze the correlation between different manually reverse mixing times and ESR.Results Be-fore specimen analysis,200 subjects were divided into 5 groups according to the manually reverse mixing for 3,6,9,12 and 15 times.The median ESR of each group was 13.0,11.5,11.0,8.0 and 11.0 mm/h in turn.Friedman test showed that there were significant differences in ESR results among the 5 groups(P＜0.05).There were significant differences in ESR results between manually reverse mixing for 3 and 6 times and man-ually reverse mixing for 12 times(P＜0.05).Spearman correlation analysis showed that there was a negative correlation between the manually reverse mixing times and ESR(r=-1.000,P=0.017).Conclusion Speci-mens can be fully mixed by manually reverse mixing for 9 times.Too few times of manually reverse mixing can lead to high ESR.Clinical laboratories should pay attention to the pre-treatment of specimens to ensure the quality of the whole test process.

Effect of Bushen Jianpi Recipe in Treating Patients with Type 2 Diabetes Mellitus Complicated with Dyslipidemia and Its Effect on Adiponectin / 广州中医药大学学报

Objective To investigate the clinical efficacy of Bushen Jianpi Recipe(mainly composed of Astragali Radix,Epimedii Folium,Dioscoreae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Cervi Cornus Colla,Astragali Complanati Semen,Polygoni Multiflori Radix Preparata,Polygonati Rhizoma,Puerariae Lobatae Radix,and Rhei Radix et Rhizoma)on patients with type 2 diabetes mellitus(T2DM)complicated with dyslipidemia and differentiated as spleen-kidney deficiency type,and to observe its effect on the level of adiponectin(ADP).Methods Ninety patients with T2DM complicated with dyslipidemia and differentiated as spleen-kidney deficiency type were randomly divided into western medicine group,Chinese medicine(CM)group,and combination of CM and western medicine group(hereinafter referred to as combination group),and each group had 30 patients.All of the 3 groups were given conventional hypoglycemic treatment.Moreover,the western medicine group was given oral use of Atorvastatin Calcium Tablets,CM group was given Bushen Jianpi Recipe,and the combination group was given Atorvastatin Calcium Tablets together with Bushen Jianpi Recipe orally.The course of treatment lasted for 8 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,glucose and lipid metabolism indexes,fasting insulin(FINS),insulin resistance index(HOMA-IR)and serum ADP levels of the three groups were observed before and after the treatment.After treatment,the efficacy of TCM syndrome of the three groups was evaluated.Results(1)After 8 weeks of treatment,the total effective rates for TCM syndrome efficacy in the western medicine group,CM group,and combination group were 66.67%(20/30),90.00%(27/30),and 93.33%(28/30),respectively.The intergroup comparison showed that the TCM syndrome efficacy of the CM group and the combination group was significantly superior to that of the western medicine group(P＜0.05).(2)After treatment,the TCM syndrome scores in all of the three groups were decreased compared with those before treatment(P＜0.01),and the decreases of the scores in both CM group and combination group was superior to that in the western medicine group(P＜0.05 or P＜0.01).(3)After treatment,the levels of lipid metabolism parameters of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)in the three groups were improved to various degrees compared with the pre-treatment levels,of which the levels of TC,TG,and LDL-C were significantly decreased,and the level of HDL-C was significantly increased in comparison with that before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The intergroup comparison showed that the decrease of TC and LDL-C and the increase of HDL-C in the CM group were inferior to those in the western medicine group and the combination group(P＜0.05 or P＜0.01).(4)After treatment,the levels of glucose metabolism parameters of fasting plasma glucose(FPG),2-hour postprandial glucose(2hPG),glycated hemoglobin(HbA1c),FINS,and HOMA-IR in the CM group and the combination group were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),while only the levels of FPG,2hPG,and HOMA-IR in the western medicine group were decreased compared with those before treatment(P＜0.05 or P＜0.01).The intergroup comparison showed that the patients in the decrease of FPG,2hPG,HbA1c,FINS,and HOMA-IR levels in the CM group and the combination group was significantly superior to that in the western medicine group(P＜0.05 or P＜0.01).(5)In terms of adipokines,the serum ADP level in the three groups after treatment was significantly increased compared with that before treatment(P＜0.05 or P＜0.01),and the increase of serum ADP level in both CM group and combination group was significantly superior to that in the western medicine group(P＜0.05).Conclusion Bushen Jianpi Recipe has certain effect on regulating lipid metabolism,and has obvious advantages in improving clinical symptoms and insulin resistance,lowering blood glucose,and increasing ADP level in patients with T2DM complicated with dyslipidemia and differentiated as spleen-kidney deficiency type.

The application of low temperature-storing tumor lumps in vitro in establishing VX2 liver cancer models:study of its modeling effect / 介入放射学杂志

Objective To compare the effect of using the fresh tumor lump and the recovered low temperature-storing VX2 tumor lump that have been frozen for different time to construct the rabbit HCC model.Methods Fish-like fresh VX2 tumor lumps were selected.After the peripheral necrotic tissue and muscle were removed,the tumor lumps were frozen at-80℃ for 3,5 and 7 months.Twenty New Zealand white rabbits were randomly divided into 4 groups.The rabbits in group A(control group)received fresh liver tumor lump implantation to construct in-situ VX2 rabbit HCC models.The rabbits in groups B,C and D(experimental groups)received implantation of the recovered low temperature-storing VX2 tumor lump which had been frozen at-80℃ for 3,5 and 7 months,respectively,to construct in-situ VX2 rabbit HCC models.Fourteen days after implantation,the modeling effect of tumor formation in each group was assessed.The proliferation,apoptosis of tumor cells and the angiogenesis were evaluated by immunofluorescence assay.Results The tumor formation rate of all group A,B,C and D was 100％.However,with the extension of cryopreservation time,the difference in tumor mass activity became larger after 5 months,and the necrotic area of liver tumor center became enlarged.Histological examination showed that there were no significant differences in the expressions of TUNEL,Ki67,HIF-α,VEGF and CD31 between group A and group B,while there were significant differences in the expressions of TUNEL,Ki67,HIF1-α,VEGF and CD31 between group A,B and group C,D.Conclusion The rabbit VX2 HCC model,which is constructed by implantation of recovered low temperature-storing VX2 tumor lump being frozen at-80℃ in vitro for a certain time,can be successfully established within 7 months.The difference in tumor mass activity between tumor lumps became larger after 5 months.But on the whole,the constructed rabbit VX2 HCC model can better preserve the tumor strain activity.This modeling technique can save manpower and material resources.(J Intervent Radiol,2024,33:269-274)

Study on Serum WWP1 and NLRP3 Expression Levels and Their Clinical Value in Patients with Heart Failure with Preserved Ejection Fraction / 现代检验医学杂志

Objective To investigate the expression level and clinical significance of WW domain-containing E3 ubiquitin protein ligase 1(WWP1)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in patients with heart failure with preserved ejection fraction(HFpEF).Methods A total of 153 patients with HFpEF admitted to Fengfeng General Hospital of North China Medical and Health Group from January 2021 to September 2022 were collected as the observation group.According to the New York Heart Association(NYHA)cardiac function grading of patients,they were grouped into cardiac function grading Ⅰ～Ⅱ group(n=64)and cardiac function grading Ⅲ～Ⅳ group(n=89),while 148 healthy volunteers were collected as the control group.The correlation between serum WWP1 and NLRP3 levels and cardiac function indexes of patients was explored by Pearson analysis.The diagnostic value of serum WWP1 and NLRP3 levels on the severity of heart failure in HFpEF patients was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the control group,the expression levels of WWP1(1.68±0.35 vs 1.04±0.19)and NLRP3(6.72±1.26 ng/ml vs 4.57±0.84 ng/ml)in the observation group were significantly increased,and the differences were statistically significant(t=19.623,17.359,all P<0.05).Compared with grade Ⅰ to Ⅱ groups,WWP1(1.87±0.39 vs 1.42±0.32)and NLRP3(7.53±1.40 ng/ml vs 5.59±1.18 ng/ml)expression levels in grade Ⅲ to Ⅳ groups were significantly increased and the differences were statistically significant(t=7.744,9.017,all P<0.05).The differences of heart rate,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic diameter(LVEDD),left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic posterior wall thickness(LVPWT),left ventricular ejection fraction(LVPWT),left ventricular ejection fraction(LVEF),peak mitral early diastolic velocity(E)/peak late diastolic velocity(A)and the incidence of atrial fibrillation between the cardiac function grade Ⅰ to Ⅱ groups and the grade Ⅲ to Ⅳ groups were significant(t/χ2=2.757～7.069,all P<0.05).Serum WWP1 level in HFpEF patients was positively correlated with LAD,LVEDD and LVPWT(r=0.547,0.471,0.536,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.485,-0.417,all P<0.05).Serum NLRP3 level was positively correlated with LAD,LVEDD and LVPWT(r=0.534,0.494,0.520,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.462,-0.523,all P<0.05).ROC results showed that the area under the curve(AUC)of serum WWP1 and NLRP3 levels alone for diagnosing the severity of heart failure in HFpEF patients was 0.825 and 0.855,respectively,and the AUC(0.924)diagnosed by the combination of the two was significantly greater than that diagnosed by the serum WWP1 alone and the AUC diagnosed by the NLRP3 alone(Z=3.600,P<0.001;Z=3.053,P=0.002).Conclusion The levels of serum WWP1 and NLRP3 were increased in patients with HFpEF,which were closely related to the cardiac function of patients.Serum WWP1 and NLRP3 have certain diagnostic value for the severity of heart failure in patients with HFpEF.

Effects of Cochlear Implantation on Ipsilateral Tinnitus in Post-lingual Adault Recipients / 听力学及言语疾病杂志

Objective To study the changes of tinnitus after cochlear implantation in post-lingual adault recip-ients and analyze the factors that affect tinnitus.Methods A total of 47 postilingually-deafened adult subjects with tinnitus who underwent cochlear implantation at the Department of Otology,the first affiliated hospital of Zheng-zhou University,from January 2017 to December 2021.The subjects were evaluated using tinnitus handicap invento-ry(THI)and visual analogue scale(VAS)before cochlear implantation and 6 months after cochlear implant surger-y.Results Among 47 subjects who were eligible for this study,the THI scores were 36.94±13.337,14.48± 12.726,respectively,before CI and 6 months after cochlear implantation.The VAS scores were 5.13±1.676 be-fore and 2.34±1.903 after cochlear tmplantation.Statistical analysis showed significant differences in THI and VAS scores before and after cochlear implantation(P＜0.05).A total of 18 patients experienced complete tinnitus suppression,14 patients experienced alleviation of tinnitus,tinnitus remained unchanged in 13 patients,tinnitus worsened in 2 patients,and the overall efficiency was 66.0％(31/47).The tinnitus alleviation rate was signifant higher in the patients with tinnitus history of ≤5 years than the patients with tinnitus history of＞5 years(P＜0.05).There was a statistically significant difference in tinnitus alleviation between the patients with mild tinnitus and the patients with more than mild tinnitus before surgery(P＜0.001).Conclusion Cochlear implantation has an inhibitory effect on tinnitus in adults.Patients with shorter duration of the tinnitus and higher tinnitus handicap are more likely to experience tinnitus improvement after cochlear implantation.

Construction of prediction model of neonatal necrotizing enterocolitis based on machine learning algorithms / 中国新生儿科杂志

Objective:To construct prediction models of necrotizing enterocolitis (NEC) using machine learning (ML) methods.Methods:From January 2015 to October 2021, neonates with suspected NEC symptoms receiving abdominal ultrasound examinations in our hospital were retrospectively analyzed. The neonates were assigned into NEC group (modified Bell's staging≥Ⅱ) and non-NEC group for diagnostic prediction analysis (dataset 1). The NEC group was subgrouped into surgical NEC group (staging≥Ⅲ) and conservative NEC group for severity analysis (dataset 2). Feature selection algorithms including extremely randomized trees, elastic net and recursive feature elimination were used to screen all variables. The diagnostic and severity prediction models for NEC were established using logistic regression, support vector machine (SVM), random forest, light gradient boosting machine and other ML methods. The performances of different models were evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, negative predictive value and positive predictive value.Results:A total of 536 neonates were enrolled, including 234 in the NEC group and 302 in the non-NEC group (dataset 1).70 were in the surgical NEC group and 164 in the conservative NEC group (dataset 2). The variables selected by extremely randomized trees showed the best predictive performance in two datasets. For diagnostic prediction models, the SVM model had the best predictive performance, with AUC of 0.932 (95% CI 0.891-0.973) and accuracy of 0.844 (95% CI 0.793-0.895). A total of 11 predictive variables were determined, including portal venous gas, intestinal dilation, neutrophil percentage and absolute monocyte count at the onset of illness. For NEC severity prediction models, the SVM model showed the best predictive performance, with AUC of 0.835 (95% CI 0.737-0.933) and accuracy of 0.787 (95% CI 0.703-0.871). A total of 25 predictive variables were identified, including age of onset, C-reactive protein and absolute neutrophil count at clincial onset. Conclusions:NEC prediction model established using feature selection algorithm and SVM classification model in ML is helpful for the diagnosis of NEC and grading of disease severity.

Optimization of 18F-FDG PET/CT semi-quantitative diagnostic model for children with autoimmune encephalitis with epilepsy and negative MRI / 中华核医学与分子影像杂志

Objective:To investigate the value of 18F-FDG PET/CT imaging in the diagnosis of suspected autoimmune encephalitis (AE) in children with epilepsy and negative MRI. Methods:From May 2019 to August 2022, 94 suspected AE children (49 males, 45 females; age 1-15 years) with epilepsy and negative MRI who underwent brain 18F-FDG PET/CT imaging at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. All patients were divided into AE and non-AE groups based on clinical final diagnosis. The effectiveness of visual diagnosis was evaluated. The cortical lesion extent score (S), and SUV max, SUV mean and minimum of SUV (SUV min) of cortical lesions (L), basal ganglia (B) and thalamus (T) were measured and SUV ratios (SUVR) of L/B or L/T were obtained. Independent-sample t test or Mann-Whitney U test was used to analyze data. Binary logistic regression analysis was used to screen the diagnostic factors of AE, and a diagnostic model was established. The diagnostic efficiency was evaluated by ROC curve analysis and Delong test. Results:There were 53 cases in AE group and 41 cases in non-AE group. Based on visual analysis, the sensitivity, specificity and accuracy of 18F-FDG PET/CT for AE were 100%(53/53), 43.9%(18/41) and 75.5%(71/94), respectively. Differences of LSUV max, LSUV mean, LSUV min, L/BSUVR max, L/BSUVR mean, L/BSUVR min, L/TSUVR max, L/TSUVR mean, L/TSUVR min and S between AE and non-AE groups were statistically significant ( z=-6.74, t values: from -8.51 to -3.97, all P<0.001). ROC curve analysis showed that the AUC of L/BSUVR max was the highest (0.914) among visual analysis and semi-quantitative parameters. Logistic regression analysis showed that S (odds ratio ( OR)=11.40, 95% CI: 2.18-59.52, P=0.004), L/BSUVR max( OR=13.19, 95% CI: 2.11-82.51, P=0.006) and L/TSUVR max( OR=9.66, 95% CI: 1.57-59.55, P=0.015) were independent diagnostic factors for AE. Regression model was established: P=1/(1+ e - x), x=2.433×S+ 2.580×L/BSUVR max+ 2.267×L/TSUVR max-3.802. The AUC of this model was 0.948, with the sensitivity, specificity and accuracy of 98.1%(52/53), 90.2%(37/41) and 94.7%(89/94), respectively. The diagnostic efficacy of the optimized scoring system was consistent with the pre-optimization model, and were both superior to L/BSUVR max(both z=2.01, both P=0.040). Conclusion:The diagnostic model and scoring system based on the semi-quantitative analysis of 18F-FDG PET/CT have better diagnostic efficacy for AE and are superior to semi-quantitative parameters alone.

Construction of hepatocyte-specific Sirt3 gene knockout mouse model / 安徽医科大学学报

Objective @#To construct hepatocyte-specific silence information regulator 3 ( Sirt3 ) gene knockout (Sirt3Δhep ) mice by Cre-loxP technique , and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases . @*Methods @#LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous (Alb-Cre + / + ) mice , and the F1 generation Sirt3flox/ - /Alb-Cre + / - mice were then mated with Sirt3flox/flox mice , and the F2 genotype of Sirt3flox/flox/Alb-Cre + / - mice were the Sirt3Δhep mice constructed in this ex- periment. Sirt3flox/flox/Alb-Cre - / - (Sirt3flox/flox ) mice were the control mice . Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice . Immunofluorescence was used to detect Sirt3 ex- pression in mouse hepatocytes . Primary hepatocytes and tissue proteins of Sirt3Δhep mice were extracted , and the ex- pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot. HE staining was used to ob- serve mice ′s liver , heart , spleen , and lung tissue structure . @*Results @#Sirt3Δhep mice were successfully identified .Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group ( P < 0. 01) . At the same time , there was no significant difference in the expression of Sirt3 in the heart , spleen , kidney , and lung tissues of Sirt3Δhep mice compared with the control group (P > 0. 05) . The results of HE staining showed that the histological characteristics of the liver , heart , spleen , lungs , kidneys , and other major organs of Sirt3Δhep mice were not significantly different from those of the control group mice . @*Conclusion @#Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed , which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases .

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Novel mechanisms driving renal tubulointerstitial fibrosis / 中国临床药理学与治疗学

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

Effects of Social Defeat Stress on Microtubule Regulating Proteins and Tubulin Polymerization

Objective@#Microtubule (MT) stability in neurons is vital for brain development; instability is associated with neuropsychiatric disorders. The present study examined the effects of social defeat stress (SDS) on MT-regulating proteins and tubulin polymerization. @*Methods@#After 10 days of SDS, defeated mice were separated into susceptible (Sus) and unsusceptible (Uns) groups based on their performance in a social avoidance test. Using extracted brain tissues, we measured the expression levels of α-tubulin, acetylated α-tubulin, tyrosinated α-tubulin, MT-associated protein-2 (MAP2), stathmin (STMN1), phospho stathmin serine 16 (p-STMN1 [Ser16]), phospho stathmin serine 25 (p-STMN1 [Ser25]), phospho stathmin serine 38 (p-STMN1 [Ser38]), stathmin2 (STMN2), phospho stathmin 2 serine 73 (p-STMN2 [Ser73]), 78-kDa glucose-regulated protein (GRP-78), and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) using Western blot assay. The tubulin polymerization rate was also measured. @*Results@#We observed increased and decreased expression of acetylated and tyrosinated α-tubulin, respectively, decreased expression of p-STMN1 (Ser16) and increased expression of p-STMN1 (Ser25), p-STMN2 (Ser73) and GRP-78 and CHOP in the prefrontal cortex and/or hippocampus of defeated mice. A reduced tubulin polymerization rate was observed in the Sus group compared to the Uns and Con groups. @*Conclusion@#Our findings suggest that SDS has detrimental effects on MT stability, and a lower tubulin polymerization rate could be a molecular marker for susceptibility to SDS.

Risk factors for healthcare-associated bloodstream infection of carbape-nem-resistant Enterobacterales / 中国感染控制杂志

Objective To analyze the characteristics and influencing factors of healthcare-associated bloodstream infection(HA-BSI)of carbapenem-resistant Enterobacterales(CRE).Methods Retrospective nested case-control study was adopted.Fifty-six patients with CRE HA-BSI in a tertiary general hospital from January 2020 to Decem-ber 2022 were selected as the CRE group.With a 1:1 ratio,56 patients with carbapenem-sensitive Enterobacterales(CSE)BSI during the same period was selected as the CSE group.Distribution of infection strains and departments was analyzed,and the relevant factors for CRE BSI were analyzed by univariate and multivariate logistic regression analyses.Results The distribution of CRE BSI was mainly in intensive care unit(ICU,n=23,41.07％)and de-partment of hematology(n=17,30.36％).The main infection strains were Klebsiella pneumoniae(n=32,57.14％)and Escherichia coli(n=16,28.57％).Univariate analysis showed that malignant tumor,hospitalization history within 60 days,stay in ICU for＞48 hours before infection,mechanical ventilation,indwelling central venous cathe-ter,combined use of at least two kinds of antimicrobial agents,and duration of antimicrobial use ≥10 days were all related to CRE BSI(all P＜0.05).Multivariate logistic regression analysis found that stay in ICU＞48 hours before infection and duration of antimicrobial use ≥10 days before infection were independent risk factors for CRE HA-BSI(P＜0.05).Conclusion Clinical departments,especially ICU,should pay attention to the epidemiological history of patients,identify patients with high-risk factors for CRE BSI as early as possible,use antimicrobial agents ratio-nally and standardize invasive procedure,so as to reduce the occurrence of CRE HA-BSI.

Hepatic lipidomics study in chronic cadmium-exposed mice / 局解手术学杂志

Objective To study the change of lipidomics in chronic cadmium-exposed mice,thereby screening out lipid subclasses,lipid molecules and enriched metabolic pathways with significant differences.Methods Twelve SPF male C57BL/6J mice(8 weeks old)were randomly divided into the control group(normal water feeding)and the experimental group[cadmium water(0.6 mg/L of CdCl2)feeding],with 6 mice in each group.Mice were sacrificed after 6 months of cadmium exposure,and fresh liver tissues were collected immediately.Lipid oil red O staining and lipidomics analysis were performed on liver tissue.Results Compared with the control group,the liver tissue of mice in the experimental group did not appear red after lipid oil red O staining.Seventeen lipid subclasses with significant differences and 144 lipid molecules with significant differences were screened out by lipidomics.These lipid molecules with significant differences were enriched in glycerophospholipid metabolism,linoleic acid metabolism,alpha-linolenic acid metabolism,glycosylphosphati-dylinositol biosynthesis,glycerolipid metabolism and arachidonic acid metabolism by KEGG.Conclusion This study reveals that chronic cadmium exposure can induce the disorder of lipid subclasses and lipid metabolites in the liver of mice,which provides a basis for understanding the non-alcoholic fatty liver disease caused by chronic cadmium exposure.

HIV screening strategies in blood donors: a cost-effectiveness analysis / 中国输血杂志

【Objective】 To analyze the cost and effectiveness of different HIV screening strategies based on multi-center HIV residual risk study, so as to provide reference for blood centers to adopt appropriate HIV testing strategies. 【Methods】 According to the HIV screening and confirmation of blood donors in three blood centers in Anhui Province, the residual risk of different HIV screening strategies was estimated. A decision tree model was established to analyze the cost-effectiveness differences of three different screening strategies under current domestic policies. 【Results】 The residual risk of anti-HIV-1 +2 ELISA, HIV Ag/Ab1+2 ELISA and ELISA+NAT were 1.17×10-6,0.84×10-6 and 0.59×10-6, respectively. According to decision tree model analysis, HIV Ag/Ab1+2 ELISA had a cost-effectiveness advantage over anti-HIV 1+2 ELISA when there was no NAT, but the advantage of HIV Ag/Ab1+2 ELISA disappeared when there was one NAT. The cost of HIV reagents, the cost of HIV treatment and the cost of false positive discarding were sensitive factors of the model. 【Conclusion】 In this area, one anti-HIV 1+2 ELISA combined with one NAT has a cost-effectiveness advantage. Blood centers need to confirm and evaluate the ELISA reagents used before conducting HIV screening. Under the premise of ensuring sensitivity, reagent cost and reagent false positive rate are the key factors.

Cerebral Glucose Metabolic Features of Parkinson's Disease Based on 18F-FDG PET:A Longitudinal Study / 中国医学影像学杂志

Purpose To establish glucose metabolism patterns of Parkinson's disease(PD)at different periods,and to study the changing pattern of target region of interest(ROI)with the period of time,and then explore the relationship between ROIs and cognitive or motor in different periods.Materials and Methods A total of 42 patients with early-stage PD collected from June 2010 to September 2022 in online data from the markers of Parkinson's progression study which included clinical data,and FDG PET imaging was performed at baseline,12,24,36 and 48 months.The data of 8 healthy volunteers were also obtained from the database,and the time range was the same as that of the above-mentioned PD patients.The longitudinal changes of cerebral glucose metabolism in PD patients and the relationship between PD-associated ROI and movement disorder society-sponsored revision of the unified Parkinson's disease rating scale(MDS-UPDRS)score were evaluated.Results PD was relatively reduced activity located in frontal and parietal association areas and relatively increased activity in the cerebellum,the putamen and the cingulate gyrus.In our study of target ROIs over time,FDG uptake in the caudate nucleus,putamen,pallidum,and cerebellum of patients with PD was initially higher than in the normal group,and subsequently decreased.In contrast,the ROI of PD in the anterior cingulate gyrus,posterior cingulate gyrus,the substantia nigra pars compacta and substantia nigra pars reticulata was initially lower than that in healthy controls and subsequently increased.The putamen,pallidum and caudate nucleus metabolic activity showed a positive correlation in 36 month and MDS-UPDRS scores(r=0.659 5,0.678 7,0.716 7,all P<0.05).The caudate nucleus,putamen and pallidum metabolic activity showed a negative correlation in 24 month and baseline(r=-0.541 8,-0.878 9,-0.887 6,all P<0.05).Conclusion We provide 5-year longitudinal data on changes in 18F-FDG imaging outcomes in early PD.In addition,the glucose metabolic activity of caudate nucleus,putamen and globus pallidus are correlated with MDS-UPDRS scores.