Nano-boron nitride (nano-BN) is a kind of nanomaterials with exceptional mechanical properties, thermal stability and electrical conductivity, and has broad application prospects in industry, energy, electronics and biomedicine. However, with the continuous expansion of its applications, the health effects and potential toxicity of nano-BN on organisms have gradually emerged, and become one of the current research hotspots of nano-BN. The toxicity studies of nano-BN will not only contribute to understanding its potential hazards but also provide crucial theoretical foundations for its safety assessment and health risk evaluation. Therefore, it is of great significance to comprehensively analyze and review the available in vivo and in vitro toxicity studies of nano-BN. This paper discussed the reported influencing factors of nano-BN toxicity, including its morphological characteristics, surface modifications, cell types, exposure dose and time, and further analyzed the oxidative stress, mitochondrial damage, DNA damage, and other related toxic mechanisms induced by nano-BN. Currently, the toxicity research of nano-BN remains limited, particularly due to insufficient human exposure data, unclear chronic toxicity in vivo, and restricted use of cell types for in vitro experiments. Future research should focus on these gaps.

Objective:To investigate the relationship between the LAMA2 gene expression and the survival time of cancer patients, tumor microenvironment, tumor immune cell infiltration, and the immunotherapy responsiveness in pan-cancer. Methods:Download the expression data matrix and the clinical data from TCGA and IMvigor210, furthermore analyze the correlation between the expression level of LAMA2 and survival time, tumor microenvironment, and immunotherapy responsiveness by R and perform the gene set enrichment analysis of LAMA2 in pan-cancer to explore the related pathways. The Wilcoxon test was used to compare the expression difference of LAMA2 between tumor tissues and normal tissues. Kaplan-Meier method was used for survival analysis, and univariate COX regression analysis was used to evaluate the risk ratio relationship of LAMA2 in various tumors. Spearman correlation analysis was used to evaluate the correlation between the expression level of LAMA2 and tumor microenvironment immune score, as well as immune cell infiltration. Pearson correlation analysis was used to evaluate the correlation between the immunotherapy responsiveness and the expression level of LAMA2. Results:Compared with normal tissues, the expression level of LAMA2 was significantly decreased in most cancer types. In addition, the up-regulation or down-regulationand of LAMA2 expression may indicate the prognosis of patients. Univariate COX regression analysis showed that LAMA2 was significantly associated with prognosis in bladder cancer, renal papillary cell carcinoma, adrenocortical carcinoma, and so on. LAMA2 expression level was also significantly correlated with tumor microenvironment score, immune score and stromal score. Furthermore, the expression level of LAMA2 was correlated with the infiltration of tumor immune cells, including B cell, CD8 + T cell, regulatory T cell, mast cell, and so on. The results of gene set enrichment analysis show that the LAMA2 was mostly involved in the biological process of ion channels, gene expression, and skeletal muscle movement. LAMA2 expression was also associated with tumor mutation burden, microsatellite instability, and cell programmed death-ligand 1 immunotherapy responsiveness. Conclusions:LAMA2 has predictive value for survival and prognosis of patients in tumors, and is significantly correlated with tumor microenvironment, immune cell infiltration, tumor microenvironment, immunotherapy responsiveness, etc. As a potential tumor marker, LAMA2 provides a new direction for tumor prognosis judgment and treatment selection.

Objective To investigate the value of radiomics nomogram model based on enhanced CT for predicting postoperative pancreatic fistula(POPF)in patients undergoing pancreaticoduodenectomy(PD).Methods The clinical and abdominal imaging data of 82 patients who underwent PD were analyzed retrospectively.They were divided into training set and validation set at a ratio of 3∶2.In the venous phase of CT,the maximum slice of the pancreatic duct was selected to delineate the region of interest(ROI),and the features were extracted and screened to construct the radiomics model.The independent risk factors associated with POPF were screened by univariate and multivariable logistic regression analyses to construct the clinical model.A nomogram model was created by combining Radiomics score(Radscore)and clinical risk factors.The diagnostic performance of the model was verified by the vali-dation set.Results The nomogram model demonstrated significant predictive power,with an area under the curve(AUC)of 0.862 and 0.806 in the training set and validation set,respectively.Conclusion The nomogram model exhibits excellent predictive performance and outperforms the clinical model and radiomics model in predicting POPF,which can provide important guidance for clinical deci-sion-making.

Objective: To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). Materials and Methods: SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Results: Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC:0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). Conclusion FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective:To explore the value of radiomics model based on intratumoral and peritumoral early dynamic contrast-enhanced (DCE) MRI for identifying benign and malignant in breast imaging reporting and data system (BI-RADS) 4 tumors.Methods:A total of 191 patients diagnosed with BI-RADS 4 breast tumors by breast MRI examination with clear pathological diagnosis from January 2016 to December 2020 in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively, including 77 benign and 114 malignant cases, aged 23-68 (46±10) years. The one-slice image with the largest area of the lesion of the second stage DCE-MRI images was selected to outline the region of interest, and automatically conformal extrapolated by 5 mm to extract the intra-tumoral and peritumoral radiomics features. The included cases were randomly divided into training and testing cohorts in the ratio of 8∶2. The statistical and machine learning methods were used for feature dimensionality reduction and selection of optimal radiomics features, and logistic regression was used as the classifier to establish the intratumoral, peritumoral, and intratumoral combined with peritumoral radiomics models. The independent risk factors that could predict the benignity and malignancy of breast tumors were retained as clinical-radiological characteristics by univariate and multivariate logistic regression to establish a clinical-radiological model. Finally, the intratumoral and peritumoral radiomics features were combined with clinical-radiological features to develop a combined model of the three. The receiver operating curve was used to analyze the predictive performance of each model and calculate the area under the curve (AUC),the AUC was compared by DeLong test. The stability of the three-component combined diagnostic model was tested by 10-fold cross-validation, and the model was visualized by plotting nomogram and calibration curves.Results:In the training cohort, the AUC of the three-component combined model for identifying benign and malignant BI-RADS 4 breast tumors was significantly higher than that of the intratumoral radiomics model ( Z=3.38, P<0.001), the peritumoral radiomics model ( Z=4.01, P<0.001), the intratumoral combined with peritumoral radiomics model ( Z=3.11, P=0.002), and the clinical-radiological model ( Z=3.24, P=0.001). And the AUC, sensitivity, specificity, accuracy, and F1-score of the three-component combined model were 0.932, 91.2%, 86.9%, 87.0% and 0.89, respectively. In the testing cohort, the three-component combined model also had the highest AUC value (0.875), and diagnostic sensitivity, specificity, accuracy and malignancy F1-score were 95.7%, 62.5%, 76.9%, and 0.89, respectively. The AUC calculated by 10-fold cross-validation was 0.90 (0.85-0.92), and the predicted curve of the three-component combined model in the calibration curve was in good agreement with the ideal curve. Conclusion:The three-component combined diagnostic model based on the intratumoral and peritumoral radiomics features and clinical-radiological features of early DCE-MRI has good performance and stability for identifying the benign and malignant in BI-RADS 4 breast tumors, and it can provide guidance for clinical decision non-invasively.

OBJECTIVE: To systematically investigate the changes rule of volatile oil and its main components released from moxa sticks under different headspace temperatures and combustion conditions, so as to guide the clinical rational selection of the temperature for moxa sticks. METHODS: Using the headspace gas chromatography-mass spectrometry (HS-GCMS) technique, the released gas from moxa sticks was collected at the headspace temperature (from room temperature [25 ℃] to 190 ℃) and during combustion. One mL of the gas was injected into 6890/5973N gas chromatography-mass spectrometry (GCMS). The release rates of volatile components of moxa sticks were calculated by total ion chromatography (TIC) and butanone internal standard method. The volatile components of moxa sticks were qualitatively analyzed by analyzing the mass spectra of each volatile component and matching the Nist 14 standard mass spectrometry library. By comparing and analyzing the peak intensity changes rule of 1,8-cineole and its main harmful components (benzene, toluene and phenol) under different headspace temperatures and combustion conditions, the optimal temperature for clinical use of moxa sticks was found. RESULTS: At room temperature and 50 ℃, the release rate of volatile components from moxa sticks was very low, and it showed a significant increase trend with the increase of temperature. When the headspace temperature was 190 ℃, the release rate of volatile components from moxa sticks reached 0.864 2%, which was 2 161 times as same as that at room temperature. After combustion, it dropped sharply to 0.027 9%, which was 96.8% lower than that at the headspace temperature of 190 ℃. When the headspace temperature was 125 ℃ and 150 ℃, the content of 1,8-cineole, a typical beneficial component in the volatile components of moxa sticks, was the highest. When the headspace temperature was higher than 150 ℃, its content showed a significant downward trend. Under combustion conditions, a large number of harmful substances, such as benzene, toluene and phenol, were detected. CONCLUSION The combustion condition is not conducive to the efficient utilization of the volatile oil of moxa sticks. Temperature of 125-150 ℃ is the best for releasing the volatile components of moxa sticks, which is not only conducive to the release of the beneficial volatile components of moxa sticks, but also can greatly inhibit the production of harmful components.
Benzene ; Eucalyptol ; Oils, Volatile ; Phenols ; Temperature ; Toluene

OBJECTIVE： To establish the method for the content determination of chlorogenic acid， ligustrazine， ferulic acid， senkyunolide I， senkyunolide H， coniferly ferulate， senkyunolide A， n-butylphtalide， Z-ligustilide and n-butylidenephthalide in Ligusticum chuanxiong under different storage conditions. METHODS： HPLC method was adopted. The determination was performed on Boston C18 column with mobile phase consisted of acetonitrile-0.5％ acetic acid solution （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 285 nm， and the column temperature was 30 ℃. The sample size was 5 μL. RESULTS： The linear range of chlorogenic acid， ligustrazine， ferulic acid， senkyunolide I， senkyunolide H， coniferly ferulate， senkyunolide A， n-butylphtalide， Z-ligustilide n-butylidenephthalide were 0.030 53-0.519 01 μg （r＝0.999 5）， 0.001 02-0.017 34 μg （r＝0.999 9）， 0.012 83-0.218 11 μg （r＝0.999 5）， 0.007 63- 0.129 71 μg （r＝0.999 7）， 0.001 76-0.029 92 μg （r＝0.999 5）， 0.054 74-0.930 58 μg （r＝0.999 9）， 0.215 80-3.668 60 μg （r＝0.999 9）， 0.018 02-0.306 34 μg （r＝0.999 7）， 0.232 50- 3.952 50 μg （r＝0.999 9）， 0.002 40-0.040 80 μg （r＝0.999 5）.The limits of quantitation were 2.073 7， 0.556 6， 0.753 8， 0.231 5， 0.306 9， 0.925 2， 2.295 3， 4.624 0， 3.215 3， 0.910 5 ng， respectively. The detection limits were 0.622 1， 0.167 0， 0.226 1， 0.069 4， 0.092 1， 0.277 6， 0.688 6， 1.387 2， 0.964 6， 0.273 1 ng， respectively. RSD of precision， stability and repeatability tests were all less than 5％ （n＝6）. The recovery rates were 95.90％-103.28％ （RSD＝2.99％， n＝6）， 88.24％-107.84％ （RSD＝4.89％， n＝6）， 95.06％-102.08％ （RSD＝3.97％， n＝6）， 93.67％-101.05％ （RSD＝1.02％， n＝6）， 94.81％-104.33％ （RSD＝2.34％，n＝6）， 94.41％-105.59％ （RSD＝4.32％， n＝6）， 92.76％-104.83％ （RSD＝1.95％， n＝6）， 87.22％-102.56％ （RSD＝2.89％， n＝6）， 94.04％-99.52％ （RSD＝0.92％， n＝6）， 88.51％-103.83％ （RSD＝4.89％， n＝6）， respectively. At 5 ℃ and 15 ℃， no obvious deterioration was observed in medicinal materials. At room temperature， some samples were moth-eaten and mildewed. The content ranges of 6 batches of samples were 0.047 7％-0.160 8％， 0.006 1％- 0.022 7％， 0.048 2％-0.172 2％， 0.023 3％-0.145 2％， 0.004 6％-0.030 7％， 0.085 2％-0.835 4％， 0.182 6％-2.112 7％， 0.009 9％- 0.098 3％， 0.614 9％-3.176 2％ and 0.005 7％-0.036 9％， showing decreasing trend； the decrease rate was in descending order 5 ℃＜15 ℃＜room temperature； at the same storage temperature， the decrease rate of polyethylene plastic bag was lower than that of polypropylene woven bag. CONCLUSIONS： This method is accurate and feasible， and can be used for simultaneous determination of 10 kinds of components in L. chuanxiong. It is suggested that L. chuanxiong medicinal materials should be sealed and packed in dry and cool places and should not be stored for a long time.

Objective To obtain a mouse CD40-specific single-chain antibody (scFv) with high purity and to investigate its in vivo and in vitro agonistic activity on natural killer(NK) cells against tumor. Methods Agonistic anti-mouse CD40 scFv with high purity was obtained by genetic engineering. Mouse dendritic cells (DCs) were treated with different strategies including anti-CD40 monoclonal antibody (McAb),anti-CD40 scFv and negative control. Expression of IL-12 in the supernatants of DC cultures was measured by ELISA. Then DCs and NK cells were co-cultured to obtain activated NK cells,which were co-cultured with T6-17 cells. WST-8 was used to test the cytotoxic effects of NK cells on T6-17 cells. A mouse tumor model was established by injecting BALB/c nude mice with T6-17 cells. Anti-CD40 scFv was injected into tumor to evaluate its inhibitory effect on tumor growth. Levels of IL-12 and IFN-γ in the tumor microen-vironment were detected by ELISA. Changes in the percentages of tumor-infiltrating NK cells and the expres-sion of NKG2D protein(natural-killer group 2,member D) were detected by flow cytometry and immunohis-tochemistry,respectively. Results The recombinant plasmid CD40 scFv-pET28a was confirmed to be con-structed correctly. Results of SDS-page and His-tag Western blot revealed that anti-CD40 scFv could be ex-pressed successfully with a relative molecular mass of 27×103. The level of IL-12 in the supernatant of DC culture of anti-CD40 scFv group was (555.86 ±40.48) pg/ml, which was significantly higher than that of negative control group (P<0.05). The killing ability of NK cells in anti-CD40 scFv group was (72.23 ± 3.99)%,which was significantly higher than that in negative control group (P<0.05). Anti-CD40 scFv significantly inhibited the tumor growth in BALB/c nude mice as compared with negative control group(P<0.05). The levels of IL-12 and IFN-γ in tumor microenvironment of anti-CD40 scFv group were(188.801± 32.718) pg/ml and(121.428±30.994) pg/ml,respectively,which were significantly higher than those in normal saline(NS) group(P<0.05). The positive rate of NKG2D protein and the percentage of CD3-DX5+cells in anti-CD40 scFv group were respectively(8.18±2.01)% and(19.15±2.24)%,which were signifi-cantly higher than those in NS group (P<0.05). Conclusion Agonistic anti-mouse CD40 scFv could en-hance the anti-tumor ability of NK cells by activating DCs.

Objective To analyze the risk factors of respiratory depression occurring during recovery period in patients after having undergone general anesthesia and laparoscopic operation.Methods A total of 374 patients after general anesthesia and laparoscopic surgery admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2015 to June 2016 were enrolled, they were divided into with or without the incidence of respiratory depression two groups by whether or not respiratorydepression, with the incidence of respiratory depression group 52 cases, without the incidence of respiratory depression group 322 cases. The patients' gender, age, body mass index (BMI), operation time, anesthesia maintenance mode, artificial airway mode, operative type and medication used in operation, intra-operative hypotension presence or absence, and type of operation were recorded. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors of respiratory depression occurring in the recovery period after general anesthesia; receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of age, intraoperative medication, and age combine with intraoperative medication respectively in the occurrence of respiratory depression during recovery period after general anesthesia and lapatoscopic operation.Results Univariate analyses showed that there were no statistical significant differences in gender, BMI, operation time, anesthesia maintenance mode, artificial airway mode, intra-operative hypotension presence or absence, type of operation, etc. compared between patients with and without the incidence of respiratory depression groups (allP > 0.05); while the differences were statistically significant in age and drug used in the operation (dezocine, flurbiprofen, dexmedetomidine or dezocine combined with dexmedetomidine, allP < 0.05). Multivariate analyses showed that age and medication used in operation were the independent risk factors for the occurrence of respiratory depression during the anesthesia recovery stage (P values being 0.000, 0.002 respectively). ROC curve showed that age, intra-operative medication and age combine with intraoperative medication respectively had certain predictive value for the occurrence of respiratory depression during the recovery period after general anesthesia and laparoscopic surgery, the area under the ROC curve (AUC) of age combine with intraoperative medicationfor prediction of occurrence of respiratory depression during recovery period after anesthesia and laparoscopic surgery was significantly larger than that of single age or single intraoperative medication (0.826 vs. 0.668, 0.750,P < 0.01), 95% confidence interval (95%CI) of age, intraoperative medication and age combined with intraoperative medication were 0.598-0.738, 0.670-0.830, 0.764-0.888, the sensitivity, specificity and accuracy rate of age combine with intraoperative medication were 53.8%, 94.4% and 88.8%, respectively.Conclusion Elderly patients undergoing general anesthesia and laparoscopic operation and dezocine, dexmedetomidine or dezocine combined with dexmedetomidine being applied in the laparoscopic operation are more easily associated with incidence of respiratory depression during recovery period of anesthesia.