Background Mercury, as a global heavy metal pollutant, poses a serious threat to human health. The toxicity of mercury depends on its chemical form. Distinguishing the forms of mercury in the environment is of great significance for mercury management and reducing human mercury exposure risks. Objective To establish a non-targeted metallomics method based on synchrotron radiation X-ray fluorescence (SRXRF) spectroscopy combined with machine learning to screen inorganic mercury (IHg) or methylmercury (MeHg) exposed rice plants. Methods Rice seeds were exposed to ultra-pure water (control group), 0.1 mg·L⁻¹ IHg (IHg group) or MeHg (MeHg group) solutions, respectively. After germination, the seedlings were cultured for 21 d, and rice leaves were collected, dried, weighed, and pressed. The content of metallome in rice leaves was determined by SRXRF. Machine learning models including soft independent modeling cluster analysis (SIMCA), partial least squares discriminant analysis (PLS-DA), and logistic regression (LR) were used to classify the SRXRF full spectra of different groups and find the best model to distinguish rice exposed to IHg or MeHg. Besides, characteristic elements were selected as input parameters to optimize the model by improving computing speed and reducing model calculation. Results The SRXRF spectral intensities of the control group, IHg group, and MeHg group were different, indicating that exposure to IHg and MeHg can interfere the homeostasis of metallome in rice leaves. The results of principal component analysis (PCA) of SRXRF spectra showed that the control group could be well distinguished from the mercury exposed groups, but the IHg group and the MeHg group were mostly overlapped. The accuracy rates of the three models (PLS-DA, SIMCA, and LR) were higher than 98% for the training set, higher than 95% for the validation set, and higher than 94% for the cross-validation set. Besides, the accuracy of the LR model was higher than that of the PLS-DA model and the SIMCA model. Furthermore, the accuracy was 92.05% when using characteristic elements K, Ca, Mn, Fe, and Zn selected by LR to distinguish the IHg group and the MeHg group. Compared with the full spectra model, although the prediction accuracy of the characteristic spectral model decreased, the input parameters of the model decreased by 99.51%, and precision, recall, and F1 score were above 84.48%, indicating that the model could distinguish rice exposed to different mercury forms. Conclusion Non-targeted metallomics method based on SRXRF and machine learning can be applied for high-throughput screening of rice exposed to different forms of mercury and thus decrease the risks of people being exposed to mercury.

Objective:To explore the effect of UMedic-Harvey simulation system in teaching cardiac auscultation.Methods:A total of 161 undergraduate students (Grade 3) who majored in clinical medicine and were enrolled in 2018 at The Second Clinical College of Wuhan University were selected as research subjects. The students were divided into reformed-teaching group ( n=40) and routine-teaching group ( n=121) to receive training in the skills presented in the "Cardiac Auscultation" chapter of the textbook Diagnostics. Before class, teachers prepared the preview resource package according to the teaching contents and objectives as well as the standardized cases in the UMedic series courses, and published the pre-class preview task through the specific learning platform. Students completed the pre-class test online. In the class, UMedic-Harvey simulation system was adopted to carry out situational simulation teaching in the reformed-teaching group, while traditional teaching mode was adopted in the routine-teaching group. After class, we conducted a post-class assessment and questionnaire survey through the learning platform and WeChat group, and collected the final examination scores of cardiac auscultation skills and electrocardiogram interpretation in the same batch of students who participated in the course of diagnostics. SPSS 25.0 was used for the t-test and chi-square test. Results:There was no significant difference in the baseline scores of cardiac auscultation skills between the two groups ( t=0.83, P=0.410). The post-class scores of cardiac auscultation skills were significantly higher for students in the reformed-teaching group than those in the routine-teaching group [(76.87±6.11) vs. (61.85±11.37), t=7.98, P<0.001]. Moreover, the final examination scores of cardiac auscultation skills were significantly higher for students in the reformed-teaching group than those in the routine-teaching group [(74.17±6.20) vs. (62.33±10.16), t=6.95, P<0.001). In addition, the final examination scores of electrocardiogram interpretation were higher for students in the reformed-teaching group than those in the routine-teaching group, but the difference was not statistically significant ( t=1.92, P=0.060). Conclusions:The application of UMedic-Harvey simulation system improves the effectiveness and quality of teaching cardiac auscultation skills.

IL-33 is a member of the IL-1 cytokine superfamily.It is a key regulator of pathological inflammation,immune ho-meostasis and fibrosis.IL-33 receptor ST2 is expressed on the surface of all innate immune cells,as well as some subtypes of B and T cells.IL-33 is a dual-function protein.Under normal circumstances,the N-terminal part of IL-33 resides in the nucleus of its ex-pressed cells and is released as a cytokine to exert immunomodulatory properties when cells are damaged or necrotic.Different expres-sion forms of IL-33 are located differently and may play different immunological roles.The immunological effects of IL-33 are highly di-verse.The cytokine IL-33 plays an amplifying and enhancing role in the innate immune response,while the full-length(FL)IL-33 stored in the nucleus inhibits inflammation by binding to NF-κB.IL-33/ST2 signaling plays a key role in both innate and acquired im-mune responses.In innate immunity,IL-33 and group 2 innate lymphocytes(ILC2)provide an important axis for rapid immune re-sponse and tissue homeostasis.In acquired immunity,IL-33 interacts with dendritic cells,Th2 cells,follicular helper T cells(Tfh)and regulatory T cells(Tregs).IL-33/ST2 signaling triggers pro-tumor or anti-tumor immune responses in different cell types in auto-crine and paracrine ways.In addition,the interaction between IL-33 and mitochondrial metabolism is also one of the potential mecha-nisms affecting the immune system.

Objective:To explore the effect of mixed reality (MR) application in the reconstruction of mandibular defects.Methods:Eighteen patients with mandibular defects were enrolled in this study, including 10 male patients and 8 female patients, whose age ranged from 27 to 45 years, and the mean age was 35.4 years. All the patients were from the Stomatological Hospital of the Fourth Military Medical University, during October 2019 to May 2021. Fibular flaps were used for the reconstruction of the mandibular defects. The patients were randomly divided into three groups, six in each group. In group one, MR-guided mandibular defect repair and reconstruction technique was used. In group two, 3D printed guide-assisted mandibular defect repair and reconstruction technique was used, and in the control group, traditional jaw defect repair and reconstruction technique was used. All the procedures were performed by the same team. Cone beam computed tomography (CBCT) was used for analysis of surgical accuracy, and questionnaires were used to evaluate the outcome of medical communication, occlusal relationship, appearance restoration, and medical experience satisfaction.Results:The mean surgical errors in the group one and group two were (1.75±0.44) mm and (1.81±0.16) mm respectively, which were both significantly lower than that in the control group (3.05±0.83) mm ( tMR=3.38, t3D=3.56, P<0.01). The medical communication (4.60±0.35, 4.52±0.28, tMR=2.90, t3D=2.77, P<0.05), occlusal relationship (4.17±0.32, 4.28±0.39, tMR=3.07, t3D=3.29, P<0.05), and medical experience satisfaction scores (4.26±0.45, 4.25±0.67, tMR=2.50, t3D=2.26, P<0.05) in the experimental groups were significantly higher than those in the control group (4.02±0.34, 3.58±0.33, 3.56±0.32, respectively). There was no significant difference in the satisfaction of appearance recovery among all the groups ( P>0.05). Conclusions:MR-guided mandibular repair and reconstruction surgery has high accuracy and is also beneficial to the recovery of occlusal relationship and medical communication.

Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE

Objective:To provide reference for clinical case diagnosis and treatment applications using descriptive analysis of patient-specific IgM and IgG test result of novel coronavirus pneumonia (COVID-19).Methods:Chemical luminescence was used to detect the levels of 423 confirmed or suspected cases IgM and IgG antibody, and the test result of patients with different clinical characteristics were compared and analyzed.Results:The positive rates of confirmed cases of COVID-19 were 80.4% (314/388) and 98.2% (381/388), for IgM and IgG respectively, and the positive rates of COVID-19 suspected cases specific IgM and IgG were 0.0% (0/24) and 45.8% (11/24), respectively. In patients at 6 weeks or more after the onset of the disease, the positive rate of IgG antibody was 100%. The level of IgG titer was generally higher in cases of 5~8 weeks after onset (mean: 112.70 AU/ml) than in cases of 1-4 weeks after onset (mean: 85.01 AU/ml) (U=8 531, P<0.0001). The level of IgG titer was higher in severe type cases than that of patients with ordinary type illness, with an average of 137.61 AU/ml. Conclusions:Specific IgM and IgG antibodies have strong application value in COVID-19 case diagnosis, and it is recommended to strengthen the tracking and monitoring of IgM and IgG titer levels in patients.

Objective To investigate effects of goal-directed fluid therapy on inflammatory cytokines under combined anesthesia.Methods 60 patients undergoing colorectal cancer surgery,aged 60 to 85 years old,which were classified as American Society of Anesthesiology(ASA)classⅡ~Ⅲ,were randomly assigned to Goal-directed fluid therapy group(group G,n = 30)and central venous pressure liquid management group(group C,n = 30). Life sign and BIS indexes were collected at the time points,before surgery(T1),after the start of the operation (T2),one hour after surgery(T3),after the operation(T4).Hemodynamic indexes were recorded.Two milliliter blood sample were phlebotomized for evaluation of TNF-α and IL-6 from each patient at T1,T3,T4.The infusion volume, the amount of bleeding,the operation time,anal exhaust time,and length of postoperative hospital stay were recorded. Results Comparing information between the two groups,infusion volume and colloid had an obvious decrease than that of group C(P<0.05).SVV and CVP of group G were much stable than group C.The levels of TNF-α and IL-6 of group G were lower than those of group C(P<0.01).The length of anal exhaust time and post-operative hospital stay group G were faster than that of group C(P<0.01).Conclusions Goal-directed fluid ther-apy is superior on fluid administration. It can reduce the release of IL-6 and TNF-α. It is beneficial to elderly colorectal cancer patients with hypertension.

ObjectiveTo explore the relationship among 25-hydroxyvitamin D,serum calcium,calcium-sensing receptor,and breast cancer. Methods The expressions of calcium-sensing receptor (CaSR) in primary breast cancer,breast benign tumors,and normal breast tissue beside tumors were determined by immunohistochemistry S-P method as well as the concentration of serum 25 (OH) D and serum calcium in breast cancer and breast benign tumors by Enzyme-linked immunosorbent assay (ELISA),Tribromoarsenazo Ⅲ method.ResultsSerum 25 (OH) D level of breast cancer was significantly lower than the breast benign tumors [ (34.13 ± 14.14) nmol/L vs (50.29 ± 25.65 ) nmol/L,t =2.870,P =0.001 ].Serum level of 25 ( OH ) D in lymph node metastasis positive patient was lower than that in negative group [ (30.8 ± 9.71 ) nmol/L vs (43.7 ± 23.59) nmol/L,t =2.467,P =0.021 ].The positive expression of CaSR in breast cancer(88.9％ )was higher than breast benign tumors(60％,x2 =6.717,P ＜ 0.01 ) and normal breast tissue beside tumors (60％,x2 =5.628,P ＜ 0.05 ).ConclusionsConcentration of serum 25 (OH)D and expression of calcium-sensing receptor in the tissues may be associated with occurrence,development and prognosis of breast cancer.

OBJECTIVE1-Bromo-3-chloro-5,5-dimethylhydantoin (BCDMH) is a solid oxidizing biocide for water disinfection. The objective of this study was to investigate the toxic effect of BCDMH on zebrafish.

METHODSThe developmental toxicity of BCDMH on zebrafish embryos and the dose-effect relationship was determined. The effect of BCDMH exposure on histopathology and tissue antioxidant activity of adult zebrafish were observed over time.

RESULTSExposure to 4 mg/L BCDMH post-fertilization was sufficient to induce a number of developmental malformations, such as edema, axial malformations, and reductions in heart rate and hatching rate. The no observable effects concentration of BCDMH on zebrafish embryo was 0.5 mg/L. After 96 h exposure, the 50% lethal concentration (95% confidence interval (CI)) of BCDMH on zebrafish embryo was 8.10 mg/L (6.15-11.16 mg/L). The 50% inhibitory concentration (95% CI) of BCDMH on hatching rate was 7.37 mg/L (6.33-8.35 mg/L). Histopathology showed two types of responses induced by BCDMH, defensive and compensatory. The extreme responses were marked hyperplasia of the gill epithelium with lamellar fusion and epidermal peeling. The histopathologic changes in the gills after 10 days exposure were accompanied by significantly higher catalase activity and lipid peroxidation.

CONCLUSIONThese results have important implications for studies on the toxicity and use of BCDMH and its analogs.

Animals ; Antioxidants ; metabolism ; Disinfectants ; toxicity ; Dose-Response Relationship, Drug ; Embryo, Nonmammalian ; drug effects ; Hydantoins ; toxicity ; Time Factors ; Water ; chemistry ; Water Pollutants, Chemical ; toxicity ; Zebrafish

Objective To investigate the expression and clinical significance of CXCR3/CXCL10in human cancer.Methods CXCR3 and CXCL10 were detected in 60 paraffinic tissues of patients with primary breast cancer,20 of mammary fibroma and 20 of mastopathy by immunohistochemistry S-P method and two stage method.Results The expression of CXCR3 (40/60,66.7％ ) and CXCL10 (45/60,75％)in breast cancer was higher than that in mastopathy [CXCR3(8/20,40％ )x2 =4.44,P =0.035 ;CXCL10( 10/20,50％ )x2 =4.36,P =0.037)].The expression of CXCR3 was related to status of axillary lymph node metastasis,clinical stage and the expression of HER-2 (x2 =4.15,P =0.042; x2 =7.74,P =0.021 ;x2 =4.27,P =0.039).The expression of CXCR3 had positive relationship to the number axillary lymph node metastasis( rs =0.375,P =0.003 ),clinical stage ( rs =0.451,P =0.000).Conclusions CXCR3 may be related to the progression and metastasis of breast cancer,and it may be used as a marker of breast cancer prognosis.