OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Objective:To develop and evaluate metal artifact removal systems (MARSs) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images.Methods:A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05).Results:Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0 mm, 1.5 mm, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively ( F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively ( F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 ( F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 ( F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 ( F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 ( F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARSs. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions:Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

Objective:To develop and evaluate metal artifact removal systems (MARS) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images.Methods:A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05).Results:Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0, 1.5, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively ( F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively ( F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 ( F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 ( F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 ( F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 ( F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARS. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions:Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

With the improvement of sanitation, the infection rate of hookworm is greatly reduced and the severe infected case is rarely reported. Combined morphological and molecular biological examinations, a severe hookworm infection patient was diagnosed in Department of Laboratorial Examination, Quanzhou First Affiliated Hospital of Fujian Medical University. The morphological methods such as direct fecal smear microscopy, saturated brine flotation and hookworm larvae culture methods were used to identify the eggs and larvae from stool samples of the patient. There were a large number of hookworm eggs in patient's stool samples, and the average count was 60 840 per gram by modified Kato method, which belonged to severe hookworm infection. Meanwhile, to distinguish the hookworm species, the semi-nested RT-PCR assay was employed to detect hookworm internal transcribed spacer series from eggs in patient's stool samples, and the result showed that the hookworm species was confirmed to be Necator americanus.
Ancylostomatoidea/genetics* ; Animals ; Feces ; Hookworm Infections/diagnosis* ; Humans ; Necator americanus/genetics* ; Polymerase Chain Reaction

Nasal preparations have unique advantages in drug delivery and are widely used in the treatment of local and systemic diseases. Nasal administration of traditional Chinese medicine （TCM） has a long history in China. In recent years， nasal preparations of TCM have attracted wide attention. Based on the information about nasal preparations of TCM from the database of National Medical Products Administration （NMPA）， Yaozh.com and China National Knowledge Internet （CNKI） in the recent 30 years， the formulation， the listed products， commonly used TCM， pharmaceutical excipients， clinical application and safety research of modern nasal preparations of TCM were summarized and expounded. Focusing on many problems in the development of modern nasal preparations of TCM， such as inaccurate dosage of some products， incomplete quality standard system of pharmaceutical excipients， imperfect safety evaluation， lack of research and development of nasal drug delivery devices and so on， the possible solutions and prospects were put forward from the aspects of optimizing the extraction and separation process of TCM， the quality control and application method of pharmaceutical excipients， the development of new dosage forms， the safety evaluation of nasal administration of TCM， and the design and development of nasal administration devices. The aim is to provide ideas for the development of nasal preparations of TCM and provide scientific basis for its sustainable utilization.

Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML), whose prognosis has been historically dismal. Given the rapid development of genomics and immunotherapies, the interference strategies for AML recurrence have been changing these years. More and more novel targeting agents that have received the U.S. Food and Drug Administration (FDA) approval for

Objective: To investigate the differential expression of serum-and-glucocorticoid-inducible-kinase-2 (SGK2) in hepatocellular carcinoma (HCC) and normal liver tissues and the related mechanism mediating signal transduction of GSK-3 β / β catenin in HCC cells. Methods: Twenty pairs of matched HCC and normal tissues were collected and the situation of expression of SGK2 mRNA was detected by real-time fluorescence quantitative PCR. Western blot was used to detect the levels of SGK2 protein in human HCC cell lines (Huh-7, SMMC-7721) and normal human liver cell line (L02). SGK2 siRNA was used to transfect human HCC cell lines (SMMC-7721 and Huh-7), and then the protein expression levels of GSK-3 β/ β - catenin was successfully detected with the above-mentioned transfected cell line by western blot. Measurement data were expressed as mean ± standard deviation (±s), and the Student t -test was used as the statistical method. Results: SGK2 mRNA expression was up-regulated in all 20 HCC samples than that of the expression of matched normal liver tissues. SGK2 protein levels were significantly higher in Huh-7 and SMMC-7721 than normal human liver cell lines (P < 0.01). The downregulation of SGK2 expression in human HCC cell lines (SMMC-7721 and Huh-7) had inhibited the expression of unphosphorylated GSK-3 β. In addition, the downregulation of SGK2 expression in HCC cell lines had decreased the dephosphorylation of β - catenin to prevent degradation of the β - catenin proteasome. Conclusion SGK2 is overexpressed in HCC and mediates GSK-3β/β- catenin signaling in HCC cells.

Objective:To compare the clinical efficacy of different doses of rabbit antithymocyte globulin (rATG) in haplo-HSCT in the treatment of hematologic malignancies.Methods:Malignant hematological patients treated at our hospital from March 2013 to December 2018 were retrospectively analyzed. These patients were divided into three groups as per three doses of ATG (6 mg/kg, 7.5 mg/kg, and 9 mg/kg) in the conditioning regimens. The transplant outcomes were compared in terms of the occurrence of acute graft versus host disease (GVHD) , infection, and survival.Results:①Total 288 patients were enrolled in the study, including 182 men and 106 women, with a median age of 18 (6-62) years. Total 110 patients were diagnosed with acute lymphoblastic leukemia (ALL) , 128 with acute myelogenous leukemia (AML) , 8 with chronic myeloid leukemia (CML) , 28 with myelodysplastic syndrome (MDS) , and 14 with mixed cell leukemia (MAL) . There were 159 patients in the ATG-6 group, 72 in the ATG-7.5 group, and 57 in the ATG-9 group. The median follow-up time of post transplantation was 14 (0.2-74) months. ②The incidence of neutrophil engraftment (96.9% , 97.2% , and 96.5% , respectively) and platelet engraftment (92.5% , 87.5% , and 86% , respectively) did not significantly differ among the ATG-6, ATG-7.5, and ATG-9 groups ( P=0.972, P=0.276) . The incidence of grades 2-4 acute GVHD was 14.5% , 11.1% , and 8.8% in the three groups, respectively ( P=0.493) , chronic GVHD incidence in the three group was 8.8% , 14.3% and 12.0% , respectively ( P=0.493) . The infection rates of CMV and EBV in the ATG-9 group (77.2% and 12.5% ) were significantly higher than those in the ATG-6 (43.3% and 3.5% ) , and ATG -7.5 group (44.4% and 1.5% ) ( P<0.001 and P=0.033, respectively) . ③Among the three groups, there were no significant difference in the 3-year overall survival [68.5% (95% CI 60.3% -77.9% ) , 60.1% (95% CI 48.3% -74.8% ) , 64.7% (95% CI 51.9% -80.7% ) ], cumulative incidences of relapse [34.6% (95% CI 34.3% -35.1% ) , 38.0% (95% CI 37.3% -38.7% ) , 20.6% (95% CI 20.0% -21.3% ) ], disease-free survival [53.3% (95% CI 44.9% -63.4% ) , 51.9% (95% CI 41% -65.8% ) , 63.9% (95% CI 51.9% -78.7% ) ] and non-relapse mortality [24.2% (95% CI 23.8% -24.5% ) , 26.0% (95% CI 25.4% -26.6% ) , 23.6% (95% CI 26.3% -28.2% ) ] ( P=0.648, P=0.165, and P=0.486 and P=0.955) . Conclusion:Low dose (6 mg/kg) of rATG may increase the risk of grade Ⅱ-Ⅳ aGVHD, and a high dose (9 mg/kg) of ATG could significantly increase the risk of CMV and EBV infection. Median dose (7.5 mg/kg) of ATG is expected to reduce the incidence of moderate to severe aGVHD and viral infections without increasing the mortality.