Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective To investigate the effect of prostaglandin family(PGs)on non-alcoholic fatty liver disease(NAFLD).Methods HepG2 cells,a human hepatocellular carcinoma cell line,were used as the research subject.The experiment was set up as a control group(Ctrl),fatty change group(FFA),prostaglandin B2(PGB2,10 μg/mL)treatment group,15-keto-prostaglandin E2(15-keto-PGE2,10 μg/mL)treatment group,and 8-iso-prostaglandin F2a(8-iso-PGF2α,10 μg/mL)treatment group.Cell activity was determined by the thiazolyl blue(MTT)assay and lipid deposition was detected by the oil red O staining.The expression levels of inflammatory factors and phosphorylated insulin receptor substrates(p-IRS)were determined by real-time fluorescence quantitative PCR(qRT-PCR)and Western blot,respectively.In addition,15 SPF-grade male C57BL/6J mice were randomly divided into a basic group(CD group,n=5,fed with 10％low-fat forage for 16 weeks),high-fat group(HFD group,n=5,fed with 60％high-fat forage for 16 weeks to model NAFLD),and PGB2 group(n=5,given 20 μg/kg PGB2 daily by tail vein injection for 2 weeks after 16 weeks of 60％high-fat diet feeding).The glucose tolerance level of the mice was detected by the intraperitoneal glucose tolerance test(IPGTT)and the degree of hepatic steatosis was determined by HE staining.Results Oil red O staining showed that PGs had no sig-nificant effect on the lipid deposition of NAFLD,but PGs were able to alleviate the inflammation associated with NAFLD.qRT-PCR re-sults showed that compared with the Ctrl group,the levels of IL-1β in the FFA group increased by 2.274±0.550 times(P=0.002 8),while under the action of 50 μg/mL PGB2,10 μg/mL 15-keto-PGE2 and 10 μg/mL 8-iso-PGF2α,the levels of IL-1β decreased to 0.720±0.036 times(P=0.003 1),0.857±0.225 times(P=0.006 4),and 1.767±0.725 times(P=0.029 7),respectively.Western blot results showed that after PGs treatment,the expression level of p-IRS protein was increased.The body weights of mice in the CD group,HFD group and PGB2 group were(28.560±2.028)g,(49.300±0.667)g,and(40.840±4.043)g,respectively,with statisti-cally significant differences between the groups(P=0.001 7).Moreover,the glucose tolerance results in the PGB2 group were better than those in the HFD group.HE staining results showed compared with the HFD group,the degree of hepatic steatosis in the PGB2 group was reduced.Conclusion PGB2,15-keto-PGE2,and 8-iso-PGF2α in the prostaglandin family can alleviate the occurrence and development of NAFLD by alleviating IL-1β-mediated inflammation,upregulating the expression of p-IRS,promoting the transmission of insulin signaling,and attenuating insulin resistance.

Objective:To explore mechanism of Fasudil reducing Aβ1-42 induced BV2 cell injury based on NLRP3 inflamma-some.Methods:BV2 cells were divided into:normal control group,Aβ stimulation group,Aβ+Fasudil intervention group,Aβ+MCC950(NLRP3 inhibitor)intervention group.Cell morphology was observed under microscope.Cell activity was determined of by CCK8.NO release was measured by Griess.NLRP3,caspase 1 and IL-18 expressions were detected by immunofluorescence staining.NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were detected by Western blot.Results:Compared with normal control group,BV2 cells in Aβ stimulation group were activated and showed amoeba-like shape,cell activity was decreased,NO production was increased,NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were increased.Fasudil intervention and MCC950 intervention inhibited cell injury induced by Aβ1-42 in which BV2 cell morphology tended to be normal,cell activity was increased,while produc-tion of NO was reduced,and NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were down-regulated,there was no significant difference between Fasudil intervention group and MCC950 intervention group.Conclusion:Fasudil may alleviate Aβ1-42 induced BV2 cell injury and inflammatory reaction by inhibiting NLRP3 inflammasome activation.

Objective To analyze the values of serum tumor necrosis factor-α stimulated gene 6 protein (TSG-6) and type ⅩⅥ collagen (col-16) in predicting the prognosis of patients with ulcerative colitis (UC). Methods A total of 160 patients with UC were enrolled as UC group, another 160 volunteers were selected as control group, and the levels of serum TSG-6 and col-16 were compared between the two groups. According to the modified Mayo scoring criteria, patients in the UC group were divided into mild group (n=63), moderate group (n=52), and severe group (n=45), and the levels of serum TSG-6 and col-16 were compared among the three groups. Based on the colonoscopy follow-up results, patients in the UC group were divided into good prognosis group (n=121) and poor prognosis group (n=39), and the levels of serum TSG-6 and col-16 were compared between the two groups. Spearman correlation analysis was used to explore the correlations of serum TSG-6 and col-16 with the modified Mayo score. Logistic regression analysis was used to investigate the impact of serum TSG-6 and col-16 on the prognosis of patients in the UC group. Receiver operating characteristic (ROC) curve was used to assess the values of serum TSG-6 and col-16 in predicting the prognosis of patients in the UC group. Results The levels of serum TSG-6 and col-16 in the UC group were significantly higher than those in the control group (P < 0.01). The levels of serum TSG-6 and col-16 in the moderate and severe groups were significantly higher than those in the mild group, and the levels of serum TSG-6 and col-16 in the severe group were significantly higher than those in the moderate group (P < 0.01). The levels of serum TSG-6 and col-16 in the poor prognosis group were significantly higher than those in the good prognosis group (P < 0.01). Spearman correlation analysis showedthat serum TSG-6 and col-16 were positively correlated with the modified Mayo score (r=0.691, P < 0.05; r=0.635, P < 0.05). Logistic analysis results showed that serum TSG-6 and col-16 were risk factors for poor prognosis (P < 0.001). ROC curve analysis showed that the areas under the curve for predicting poor prognosis in patients with UC were 0.773 and 0.765 for serum TSG-6 and col-16, respectively. Conclusion The levels of serum TSG-6 and col-16 are abnormally elevated in patients with UC, and there is a certain correlation of the two indexes with the severity and prognosis of disease, and the two indexes can be used as predictors of poor prognosis.

Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.
Animals ; Mice ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor ; Apoptosis/genetics* ; bcl-2-Associated X Protein ; Caspase 3 ; Cognition ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondrial Dynamics/genetics*

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Objective:To document the clinical efficacy of using electrical stimulation to guide acupuncture on the peroneal longus and the peroneal brevis of patients with functional ankle instability (FAI).Methods:Seventy FAI patients were randomly divided into an observation group and a control group, each of 35. Both groups received routine balance function training, proprioception training and manual activation of the peroneal muscles. The observation group also received acupuncture at the motor points of the peroneal longus and the peroneal brevis muscles under the guidance of electrical stimulation, once a day, for 3 weeks. Before and after the treatment, any curative effect was quantified using the CAIT ankle instability assessment questionnaire, electromyography (iEMG) of the peroneal longus and the peroneal brevis, as well as those muscles′ excitation times during simulated varus walking.Results:All of the measurements after the treatment were significantly better than before the treatment, with the improvements in the observation group significantly greater than in the control group.Conclusions:Acupuncture at the motor points of the peroneal longus and the peroneal brevis under the guidance of electrical stimulation can effectively activate the related muscles and relieve the symptoms of functional ankle instability.

Objective:To understand the epidemic characteristics and influential factors of brucellosis patients in Laizhou, Shandong Province, and to provide scientific basis for prevention and control of brucellosis.Methods:Retrospective analysis was conducted to collect the surveillance data and epidemiological investigation results of confirmed cases of brucellosis in Laizhou from 2016 to 2019 through the "Infectious Disease Report Information Management System of the China Disease Prevention and Control Information System". The general situation, epidemiological characteristics, and clinical characteristics of brucellosis were analyzed by descriptive epidemiology. Using the case-control study method, 81 confirmed cases of brucellosis and 162 healthy people in the same area, same gender and same age as confirmed cases were selected to analyze the influential factors of brucellosis.Results:Totally 222 cases of brucellosis had been reported in Laizhou, with an average annual incidence of 6.57/100 000. The onset age of brucellosis was mainly from 45 to 59 years old, accounting for 46.40% (103/222); male-to-female ratio was 2.42 ∶ 1.00 (157 ∶ 65); the occupation distribution was mainly farmer, accounting for 95.95% (213/222). The onset time of brucellosis was mainly from March to July, accounting for 58.11% (129/222). Cases of brucellosis were reported in 17 townships (streets) of Laizhou, and the top five townships were Zhuqiao, Shahe, Tushan, Chengguo and Yidao towns in order of incidence. Among 222 cases of brucellosis, the shortest interval from onset to diagnosis was 5 d, the longest was 36 d, and the median was 11 d. The main clinical manifestations of the patients were fever (89.19%, 198/222), fatigue (80.63%, 179/222), joint muscle soreness (72.97%, 162/222), and a few accompanied by liver, spleen and testis enlargement. The logistic regression analysis showed that contact with urine, feces and other excrements of diseased animals [odds ratio ( OR) = 6.244, 95% confidence interval ( CI): 1.609 - 24.231] and family members suffering from brucellosis ( OR = 16.363, 95% CI: 2.250 - 119.023) were risk factors of brucellosis. Conclusions:The incidence of brucellosis is mainly among 45 - 59 middle-aged farmers in Laizhou and the incidence peaks in spring and summer. Direct contact with excrements of diseased animals and family members suffering from brucellosis are the risk factors of brucellosis. Health departments should carry out health education and behavioral intervention for farmers in the season and areas with high incidence of brucellosis, so as to improve personal awareness of protection.

Objective:To analyze the epidemiological characteristics of human brucellosis (referred to as brucellosis) from 2011 to 2018 in Yantai City, and to provide scientific basis for formulating and adjusting brucellosis prevention and control strategies.Methods:Descriptive epidemiological method was used to analyze the monitoring data and epidemiological survey data (time, area, population distribution and treatment behavior) of brucellosis in Yantai from 2011 to 2018.Results:From 2011 to 2018, 795 cases of brucellosis were reported in Yantai, with an annual incidence of 1.42/100 000 and no deaths. Most of the cases were sporadic, accounting for 92.20% (733/795). The incidence peak was from March to August, accounting for 67.80% (539/795). In addition to Changdao County, cases of brucellosis had been reported in 12 counties (cities, districts). The incidence rate of the top three counties (cities, districts) were 5.20/100 000 (369 cases, accounting for 46.42%) in Laizhou City, 2.13/100 000 (97 cases, accounting for 12.20%) in Zhaoyuan City, and 1.77/100 000 (62 cases, accounting for 7.80%) in Penglai City. The male and female sex ratio was 2.82 to 1.00 (587 to 208). The age of onset was mainly 40 - 69 years old, accounting for 79.62% (633/795). Occupation was mainly farmers, accounting for 83.90% (667/795). Cases were mainly found in local medical institutions, accounting for 89.56% (712/795). The average interval between onset and diagnosis was 17 days, the longest was 40 days in 2012, and the shortest was 12 days in 2018.Conclusions:From 2011 to 2018, except Changdao County, 12 counties (cities and districts) in Yantai City had reported brucellosis cases. The incidence peak was in spring and summer, mainly in middle-aged and elderly people, so we should carry out targeted prevention and control strategies for different areas and key populations.