Objective To explore the expression differences of the docking protein 1(DOK1)gene in multiple tissues of mice during the development stage from prediabetes to type 2 diabetes mellitus(T2DM),as well as its correlation with blood lipid levels.Methods The mice were divided into the 0 d group(control),the 20 d group,the 40 d group,the 60 d group,the 80 d group and the T2DM group.The 0 d group was fed with normal diet,while the other four groups were fed with high-fat diet to establish the prediabetes model.On this basis,the T2DM group was given low-dose multiple intraperitoneal injections of streptozotocin(STZ)to establish the T2DM model.The fasting and intraperitoneal glucose tolerance test(IPGTT)and insulin tol-erance test(IPITT)blood glucose of mice in each group were detected,and the expression of the DOK1 gene in nine tissues(heart,liver,kidney,skeletal muscle,pancreas,adipose,spleen,lung and colon tissues)was de-tected by qPCR.The level of DOK1 in serum was determined by ELISA,and the lipid level in serum was measured by an automatic biochemical analyzer.The correlations between serum DOK1 and TG,TC,HDL-C,LDL-C,lipoprotein A[LP(a)],and free fatty acids(FFA)were analyzed by Spearman correlation analysis.Re-sults The prediabetic and T2DM model mice were successfully established.Compared with the 0 d group,the blood glucose and lipid levels in the 80 d group and the T2DM group were significantly increased(P<0.001).Compared with the 0 d group,the expression level of DOK1 mRNA in the T2DM group was significantly de-creased in heart,liver,kidney,skeletal muscle,pancreas and adipose tissue(P<0.05).Compared with the 0 d group,the expression level of DOK1 mRNA in the 80 d group was significantly decreased in heart,liver,kid-ney and skeletal muscle tissue(P<0.05).Compared with the 0 d group,the expression levels of DOK1 mR-NA in the 40 d group and the 60 d group was significantly decreased in the liver tissues(P<0.05).Compared with group 0 d,there was no statistically significant difference in the expression level of DOK1 mRNA in the spleen,lung and colon tissues among each group(P>0.05).DOK1 in the 80 d group and the T2DM group was negatively correlated with TG,TC,LDL-C,LP(a),and FFA(r=-0.787 8,-0.727 2,-0.763 7,-0.764 2,-0.892 5,P<0.001),while positively correlated with HDL-C(r=0.961 3,P<0.001).Conclu-sion The reduction of DOK is related to the mechanism of insulin resistance and may play a key role in lipid metabolism disorders associated with diabetes.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

An automated identification method for adolescent schizophrenia based on brain electroencephalogram(EEG)entropy features is proposed for further improving the diagnostic accuracy of adolescent schizophrenia.The raw EEG signals are decomposed into 5 commonly used rhythm bands:Delta,Theta,Alpha,Beta,and Gamma.The permutation entropy,fuzzy entropy,and sample entropy are extracted from each rhythm band and then organized into a feature matrix structured by electrode location×frequency band.Finally,an ECA-CNN model integrating efficient channel attention(ECA)and convolutional neural network(CNN)is constructed for feature classification and realizing the automated identification of adolescent schizophrenia.The results demonstrate that the proposed ECA-CNN model has higher recognition accuracy than the traditional machine learning models,achieving an accuracy of 99.08%,a sensitivity of 99.27%,a specificity of 98.85%,a precision of 99.01%,a F1 score of 99.14%,and a Kappa coefficient of 0.9814.This study provides a new idea and method for the diagnosis of adolescent schizophrenia.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

An automated identification method for adolescent schizophrenia based on brain electroencephalogram(EEG)entropy features is proposed for further improving the diagnostic accuracy of adolescent schizophrenia.The raw EEG signals are decomposed into 5 commonly used rhythm bands:Delta,Theta,Alpha,Beta,and Gamma.The permutation entropy,fuzzy entropy,and sample entropy are extracted from each rhythm band and then organized into a feature matrix structured by electrode location×frequency band.Finally,an ECA-CNN model integrating efficient channel attention(ECA)and convolutional neural network(CNN)is constructed for feature classification and realizing the automated identification of adolescent schizophrenia.The results demonstrate that the proposed ECA-CNN model has higher recognition accuracy than the traditional machine learning models,achieving an accuracy of 99.08%,a sensitivity of 99.27%,a specificity of 98.85%,a precision of 99.01%,a F1 score of 99.14%,and a Kappa coefficient of 0.9814.This study provides a new idea and method for the diagnosis of adolescent schizophrenia.

Objective:To investigate the risk factors of olfactory dysfunction (OD) of female patients with primary Sj?gren′s syndrome (pSS) and a prediction model was constructed.Methods:A total of 252 female pSS patients in the Third Municipal Hospital of Huzhou, from January 2021 to 2023 were recruited. According to the olfactory function,they were divided into OD group (144 cases) and without OD group (108 cases).The independent risk factors of OD were evaluated and the clinical prediction efficiency of the model was analyzed by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and the decision curve analysis (DCA) curve.Results:The rate of OD was 57.1%((144/252)) in female pSS patients. Hyposmia was the main olfactory disorder in OD group (140/144, 97.2%). Univariate analysis showed that there were significant differences between OD and without OD groups, including disease course ( t=-2.05, P=0.040), RF( t=2.90, P=0.004), IgG( t=4.41, P=0.001), C3( t=5.47, P=0.001), ESSPRI( t=2.55, P=0.011), ESSDAI( t=3.80, P=0.001), HAMD ( t=3.38, P=0.001). Logistic regression analysis showed that high serum RF, IgG and low complement 3, high scores of ESSDAI and HAMD high scores were independent risk factors for pSS patients with OD patients[ OR(95% CI)=1.01(1.01, 1.03), 1.21(1.06, 1.38), 0.98(0.96, 0.89), 1.52 (1.20, 1.92), 1.13(1.03, 1.23)] ( P value were 0.016, 0.005, 0.004, <0.001 and 0.007 respectively). Based on the above independent risk factors, we constructed the prediction model nomogram and performed the internal data validation. The ROC curve AUC (95% CI) of the modeling group was 0.83(0.77, 0.89) and validation group was 0.69(0.57, 0.82), the prediction model was well differentiated.Hosmer-Lemeshow goodness-of-fit test showed that the prediction model had good calibration ability ( P=0.083), and the DCA curve display model is clinically valuable. Conclusion:The clinical prediction model developed in this study can be used to assess the risk of pSS-OD development, which is helpful for early detection and timely interention so can improve the quality of life of pSS-OD patients in turn.

Objective To investigate the clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95％CI 0.758～0.918),0.774(95％CI 0.656～0.892),and 0.700(95％CI 0.589～0.810),respectively,and the value of their combined model was 0.899(95％CI 0.811～0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71％and 86.52％,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P＜0.001,95％CI 0.140～0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.

Objective To study the relationship between lipid metabolism and liver function indexes in prediabetic population,and explore the predictive value of these indexes for prediabetes.Methods 546 patients with prediabetes who underwent physical examination in the First Affiliated Hospital of Xi'an Jiaotong University from April 2020 to August 2021 were selected as case group(PreDM group)and 546 patients with normal glucose tolerance as control group(NGT group).There was no significant difference in baseline data between the two groups after tendency matching score.The levels of lipid metabolism and liver function indicators were compared between the two groups;the correlation between lipid metabolism and liver function indicators in the PreDM group was analyzed;the influencing factors of prediabetes were screened by using binary logistic regression analysis;the predictive effect of lipid metabolism and liver function indicators on prediabetes was judged by using the ROC curve.Results Glutamic pyruvic transaminase(ALT),glutamic pyruvic transaminase/glutamic oxaloacetic transaminase ratio(ALT/AST),cholinesterase(CHE),gamma glutamyltransferase(GGT),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),total cholesterol/high density lipoprotein cholesterol ratio(TC/HDL-C)and triglyceride/high density lipoprotein cholesterol ratio(TG/HDL-C)in PreDM group were higher than those in NGT group(all P＜0.05).Spearman correlation analysis showed that TG/HDL-C in PreDM group had the positive correlation with ALT,ALT/AST,CHE and GGT(r=0.256,0.256,0.293,0.122,all P＜0.05).Multivariate stepwise logistic regression analysis showed that ALT/AST,GGT,TC/HDL-C and TG/HDL-C had the greatest effect on prediabetes(OR=2.124,1.027,1.196,1.260),and the combination of the four had the highest differential diagnostic value(AUC＞0.70).Conclusion There are more abnormal indexes of blood lipid and liver zymogram in prediabetic population,and the combination of ALT/AST,GGT,TC/HDL-C and TG/HDL-C is more effective in predicting prediabetes.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.