Voltage-gated sodium (Nav) channels are indispensable membrane elements for the generation and propagation of electric signals in excitable cells. The successes in the crystallographic studies on prokaryotic Nav channels in recent years greatly promote the mechanistic investigation of these proteins and their eukaryotic counterparts. In this paper, we mainly review the progress in computational studies, especially the simulation studies, on these proteins in the past years.
Ion Channel Gating ; Ligands ; Models, Biological ; Permeability ; Substrate Specificity ; Voltage-Gated Sodium Channels ; chemistry ; metabolism

An atmospheric pressure chemical ionization mass spectrometry (APCI-MS) method was developed for the direct analysis of triglycerides in edible oils.The edible oil sample was dissolved in acetonitrile.Under the optimal conditions such as positive ion detection,800 μL/h of sample flow rate,250℃ of vaporizer temperature and 5000 nA of corona needle current,the repeatability (RSD) of peak intensity rate of m/z 857.76 to m/z 881.76 was less than 5％.Then,different kinds of oil from different manufacturers were analyzed by the proposed method.After a principal component analysis for the analytical results,the peak intensity rate of m/z 857.76 and m/z 881.76 was selected for oil identification.The adulteration of 5％ lard in corn oil could be recognized directly using the peak intensity rate.Three characteristic triglycerides in edible oil were preliminarily identified by collision induced dissociation (CID) experiments.The method was applied to analyze the swill oil and fried oil samples,and the results showed that the swill oil contained both vegetable oil and animal fat,and the fried oil was also different with commercial vegetable oil.

Objective:To analyze the epidemiological characteristics, clinical characteristics and blood purification effect of mushroom poisoning in children.Methods:A retrospective study was conducted on 51 children with acute mushroom poisoning admitted to Hunan Children′s Hospital from 2002 to 2020.The epidemiological and clinical characteristics were analyzed, and the prognosis of children with different incubation periods was analyzed and compared.Among them, 36 critically ill children were treated with blood purification.Results:The age distribution was 66(43, 115)months.Mushroom poisoning had obvious seasonal and spatial aggregation.The first symptom was mainly manifested by digestive tract, which was manifested as vomiting, abdominal pain and diarrhea, accounting for 94.1% patients(48/51). The gastrointestinal tract type accounted for 45.1%(23/51) of the clinical types and the multi-organ damage type accounted for 51.0% patients(26/51). The length of hospital stay was 6(3, 11)days.Among them, early onset accounted for 45.1% patients(23/51), late onset accounted for 54.9% patients(28/51). Early onset hospitalization was shorter, about 4(2, 7)days, and fewer organs 1(0, 3) were damaged.The length of hospital stay of late onset was 8(3, 12)days, and the number of damaged organs was 4(2, 4). There was a statistically significant difference( P<0.05). Late onset patients had more severe organ function damage, including liver function, coagulation function, renal function, myocardial enzyme, and there was no significant difference in the final outcome between two groups.In 36 children who were given blood purification treatment, alanine aminotransferase, aspartate aminotransferase, prothrombin time, international normalized ratio, blood urea nitrogen, and lactate dehydrogenase were significantly improved, with statistically significant differences( P<0.05). Conclusion:Mushroom poisoning has obvious seasonal and geographical distribution characteristics; the first manifestation is mainly gastrointestinal symptoms; the clinical types are more common in gastrointestinal and multiple organ damage types.Children with early onset have shorter hospital stays and fewer complications than later onset.Blood purification treatment can significantly improve liver function, kidney function and blood coagulation function in children with toadstool poisoning.

Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.

Objective:To develop a Work Pressure Scale for Postpartum Returning Nurses, and test its reliability and validity.Methods:Based on the theory of "cognition-phenomenology-interaction", we established the item pool by combining the qualitative interview. The initial scale was formed after expert consultation and pre-investigation. We selected 282 postpartum returning nurses for the item analysis and exploratory factor analysis, and selected 635 postpartum returning nurses for the reliability and validity test.Results:The formed Work Pressure Scale for Postpartum Returning Nurses included 5 dimensions and 30 items, and the content validity was 0.943. The correlation coefficients among the scale, Self-rating Depression Scale and McCloskey/Mueller Satisfaction Scale were 0.572 and -0.482 respectively with statistical differences ( P<0.01) . The exploratory factor analysis showed that the cumulative variance contribution rate was 59.379%, and confirmatory factor analysis showed that the 5-factor model had a good fit. The Cronbach's α coefficient of the scale was 0.940 and the half-reliability was 0.882. Conclusions:The Work Pressure Scale for Postpartum Returning Nurses has good reliability and validity which can be used to evaluate the work pressure of postpartum returning nurses.

Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)?like features. Methods Five cases of DDLPS with IMT?like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People′s Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space?occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle / polygonal /stellate?shaped cells arranged in storiform, sheet?like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well?differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK?1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow?ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions DDLPS with IMT?like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low?grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low?grade myofibroblastic sarcoma, and low?grade fibrosarcoma.

Objective:To study the influence of different region of interest (ROI) sketch on measurement results in the diagnosis of breast cancer by imaging technology of intravoxel incoherent motion (IVIM) .Methods:The clinical dataes of 84 patients with breast mass lesions from Apr. 2017 to Oct. 2021 were collected, all patients underwent IVIM-DWI. ROI was delineated at the maximum level of the mass by tumor contour method and fixed radius method. The apparent diffusion coefficient (ADC), real diffusion coefficient (D), perfusion fraction (f) and pseudo diffusion coefficient (D *) were recorded. IVIM-DWI parameters of patients with benign and malignant breast tumors were compared. The influence of ROI delineation by tumor contour method and fixed radius method on the results of IVIM related parameters were compared. Results:Forty-six of 84 patients were malignant and 38 benign masses. The ADC and D values of patients in the malignant group were (0.98±0.24) ×10 -3 mm 2/s, (0.79±0.22) ×10 -3 mm 2/s in the malignant group, significantly lower than those in the benign group [ (1.65±0.43) ×10 -3 mm 2/s, (1.41±0.35) ×10 -3 mm 2/s], and the f value and D * value were (5.65±1.13) %, (43.89±8.05) ×10 -3 mm 2/s, significantly higher than those in the benign group [ (3.84±1.57) %, (37.77±9.3) ×10 -3 mm 2/s]. The differences were statistically significant ( t=9.01, 9.89, 6.13, 3.23; all P<0.05). The results obtained by using the tumor fixed radius method to delineate ROI showed that the ADC and D values of (0.96±0.27) ×10 -3 mm 2/s (0.81±0.23) ×10 -3 mm 2/s in the malignant group were significantly lower than those in the benign group [ (1.66±0.39) ×10 -3 mm 2/s, 1.39±0.37) ×10 -3 mm 2/s], and the f and D * values were (5.69±1.15) %, (43.94±7.98) ×10 -3 mm 2/s, which were significantly higher than those in the benign group [ (3.86±1.49) %, (38.01±8.46) ×10 -3 mm 2/s]. The differences were statistically significant ( t=9.69, 8.78, 6.35, 3.30; all P<0.05) .The 95% consistency interval range of ADC difference, D value difference, f value difference, and D * value difference obtained by using tumor contour method to delineate ROI was smaller than that of tumor fixed radius method. Conclusions:The IVIM has high accuracy in the diagnosis of breast cancer, the IVIM parameters obtained from ROI delineation by tumor contour method have good repeatability.

Animals ; Antimicrobial Cationic Peptides ; chemistry ; pharmacology ; Fluorescence Resonance Energy Transfer ; Humans ; Peptide Chain Elongation, Translational ; drug effects ; Single Molecule Imaging

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)-like features. Methods: Five cases of DDLPS with IMT-like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People′s Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results: All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space-occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle/polygonal/stellate-shaped cells arranged in storiform, sheet-like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well-differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK-1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow-ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions DDLPS with IMT-like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low-grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low-grade myofibroblastic sarcoma, and low-grade fibrosarcoma.

Objective To study changes in bone microstructure of osteoporotic rats by multiscale analysis. Methods A total of 20 5-month-old female SD rats were randomly divided into two groups, i.e., ovariectomy (OVX) group (n=12) and the SHAM group (n=8), respectively. The rats in OVX group were subjected to bilateral ovariectomy and became osteoporosis models after 8 weeks, while sham operation was performed for the SHAM group. Changes in microstructure of cortical bone and cancellous bone at tissue scale, and osteocyte lacunar-canalicular network (LCN) and extracellular matrix (ECM) at cell scale were quantitatively analyzed using Micro-CT and SR-Nano-CT. Results At tissue scale, the cross-sectional area of cortical bone in OVX group was significantly higher than that in SHAM group (P<0.05), and the bone mineral density (BMD) and thickness of cortical bone were not significantly different from those in SHAM group. The trabecular BMD, bone volume fraction, trabecular thickness and trabecular number in OVX group were significantly decreased in comparison with SHAM group (P<0.01), while the trabecular separation was significantly increased (P<0.01). At cell scale, there was no significant difference in the semiaxes of lacunae between OVX group and SHAM group, but the thickness of lacunae and the diameter of canaliculi in OVX group were significantly increased in comparison with SHAM group (P<0.05). At the same time, the porosity of cortical bone in OVX group was significantly higher than that in SHAM group at cell scale (P<0.05). Conclusions The bone microstructure in OVX group varied to different extents at tissue and cell scales. At tissue scale, the cancellous bone loss was severe, while the cortical bone had fewer changes. At cell scale, porosity of the lacunar-canalicular network significantly increased, which directly affected the BMD and strength of cortical bone. Multiscale analysis on changes in bone microstructure of OP rats has potential application value for clinical diagnosis and pathological analysis of osteoporosis.