Silencing CD28 attenuated chest blast exposure-induced traumatic brain injury through the PI3K/AKT/NF-κB signaling pathway in male mice.

In modern war or daily life, blast-induced traumatic brain injury (bTBI) is a growing health concern. Our previous studies demonstrated that inflammation was one of the main features of bTBI, and CD28-activated T cells play a central role in inflammation. However, the mechanism of CD28 in bTBI remains to be elucidated. In this study, traumatic brain injury model induced by chest blast exposure in male mice was established, and the mechanism of CD28 in bTBI was studied by elisa, immunofluorescence staining, flow cytometry analysis and western blot. After exposure to chest shock wave, the inflammatory factors IL-4, IL-6 and HMGB1 in serum were increased, and CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung were activated. In addition, chest blast exposure resulted in impaired spatial learning and memory ability, disruption of the blood-brain barrier (BBB), and the expression of Tau, p-tau, S100ß and choline acetyltransferase were increased. The results indicated that genetic knockdown of CD28 could inhibit inflammatory cell infiltration, as well as the activation of CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung, improve spatial learning and memory ability, and ameliorate BBB disruption and hippocampal neuron damage. Moreover, genetic knockdown of CD28 could reduce the expression of p-PI3K, p-AKT and NF-κB. In conclusion, chest blast exposure could lead to bTBI, and attenuate bTBI via the PI3K/AKT/NF-κB signaling pathway in male mice. This study provides new targets for the prevention and treatment of veterans with bTBI.

Influencing factors of hospitalization cost of hypertension patients in traditional Chinese medicine hospitals.

Objectives: This study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension. Methods: In this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively. Results: The results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor. Conclusion: The Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients.

Tumor conspicuity enhancement-based segmentation model for liver tumor segmentation and RECIST diameter measurement in non-contrast CT images.

BACKGROUND AND OBJECTIVE: Liver tumor segmentation (LiTS) accuracy on contrast-enhanced computed tomography (CECT) images is higher than that on non-contrast computed tomography (NCCT) images. However, CECT requires contrast medium and repeated scans to obtain multiphase enhanced CT images, which is time-consuming and cost-increasing. Therefore, despite the lower accuracy of LiTS on NCCT images, which still plays an irreplaceable role in some clinical settings, such as guided brachytherapy, ablation, or evaluation of patients with renal function damage. In this study, we intend to generate enhanced high-contrast pseudo-color CT (PCCT) images to improve the accuracy of LiTS and RECIST diameter measurement on NCCT images. METHODS: To generate high-contrast CT liver tumor region images, an intensity-based tumor conspicuity enhancement (ITCE) model was first developed. In the ITCE model, a pseudo color conversion function from an intensity distribution of the tumor was established, and it was applied in NCCT to generate enhanced PCCT images. Additionally, we design a tumor conspicuity enhancement-based liver tumor segmentation (TCELiTS) model, which was applied to improve the segmentation of liver tumors on NCCT images. The TCELiTS model consists of three components: an image enhancement module based on the ITCE model, a segmentation module based on a deep convolutional neural network, and an attention loss module based on restricted activation. Segmentation performance was analyzed using the Dice similarity coefficient (DSC), sensitivity, specificity, and RECIST diameter error. RESULTS: To develop the deep learning model, 100 patients with histopathologically confirmed liver tumors (hepatocellular carcinoma, 64 patients; hepatic hemangioma, 36 patients) were randomly divided into a training set (75 patients) and an independent test set (25 patients). Compared with existing tumor automatic segmentation networks trained on CECT images (U-Net, nnU-Net, DeepLab-V3, Modified U-Net), the DSCs achieved on the enhanced PCCT images are both improved compared with those on NCCT images. We observe improvements of 0.696-0.713, 0.715 to 0.776, 0.748 to 0.788, and 0.733 to 0.799 in U-Net, nnU-Net, DeepLab-V3, and Modified U-Net, respectively, in terms of DSC values. In addition, an observer study including 5 doctors was conducted to compare the segmentation performance of enhanced PCCT images with that of NCCT images and showed that enhanced PCCT images are more advantageous for doctors to segment tumor regions. The results showed an accuracy improvement of approximately 3%-6%, but the time required to segment a single CT image was reduced by approximately 50 %. CONCLUSIONS: Experimental results show that the ITCE model can generate high-contrast enhanced PCCT images, especially in liver regions, and the TCELiTS model can improve LiTS accuracy in NCCT images.

Study on the effect of licochalcone A on intestinal flora in type 2 diabetes mellitus mice based on 16S rRNA technology.

Licorice, has a long history in China where it has various uses, including as a medicine, and is often widely consumed as a food ingredient. Licorice is rich in various active components, including polysaccharides, triterpenoids, alkaloids, and nucleosides, among which licochalcone A (LicA) is an active component with multiple physiological effects. Previous studies from our research group have shown that LicA can significantly improve glucose and lipid metabolism and related complications in Type 2 diabetes mellitus (T2DM) mice. However, research on the mechanism of LicA in T2DM mice based on intestinal flora has not been carried out in depth. Therefore, in this study, LicA was taken as the research object and the effects of LicA on glucose and lipid metabolism and intestinal flora in T2DM mice induced by streptozotocin (STZ)/high-fat feed (HFD) were explored. The results indicated that LicA could reduce serum TC, TG, and LDL-C levels, increase HDL-C levels, reduce blood glucose, and improve insulin resistance and glucose tolerance. LicA also alleviated pathological damage to the liver. The results also showed that LicA significantly affected the intestinal microbiota composition and increased the α diversity index. ß Diversity analysis showed that after the intervention of LicA, the composition of intestinal flora was significantly different from that in the T2DM model group. Correlation analysis showed that the changes in glucose and lipid metabolism parameters in mice were significantly correlated with the relative abundance of Firmicutes, Bacteroidetes, Helicobacter, and Lachnospiraceae (p < 0.01). Analysis of key bacteria showed that LicA could significantly promote the growth of beneficial bacteria, such as Bifidobacterium, Turicibacter, Blautia, and Faecococcus, and inhibit the growth of harmful bacteria, such as Enterococcus, Dorea, and Arachnococcus. In conclusion, it was confirmed that LicA reversed the imbalanced intestinal flora, and increased the richness and diversity of the species in T2DM mice.

Choroidal Vortex Vein Drainage System in Central Serous Chorioretinopathy Using Ultra-Widefield Optical Coherence Tomography Angiography.

Purpose: To evaluate differences in the choroidal vortex vein drainage system (VV) in eyes between patients with central serous chorioretinopathy (CSC) and unaffected individuals using ultra-widefield optical coherence tomography angiography (UWF-OCTA). Methods: In this cross-sectional observational study, 40 eyes of patients with CSC and 28 eyes of healthy volunteers were included. The analysis involved the use of UWF-OCTA to analyze the proportion of the choroidal vortex vein drainage system (VV%), choroidal thickness, choroidal vascular volume (CVV), and choroidal vascularity index (CVI) of the VV in each drainage quadrant. The location relationship between the leakage points in fluorescein angiography and the VV was also explored. Results: A within-group analysis of VV% showed a statistically significant difference in the CSC group (P < 0.001) but not in the control group (P = 0.270). Compared to healthy eyes, CSC eyes had a significantly larger CVV and higher CVI in all regions (all P < 0.05). The superotemporal (ST) drainage system had the largest CVV and thickest choroidal layer among the four drainage quadrants (all P < 0.05) in CSC eyes. The leakage rate in the ST quadrant was significantly higher than that in the inferotemporal quadrant (P < 0.001). Conclusions: CSC eyes have an asymmetric vortex vein drainage system, with relative hyperperfusion in all VV. Further, the preferential drainage route of the submacular choroid may be the ST drainage system in CSC eyes. Translational Relevance: Targeting the imbalanced drainage system could be a potential therapeutic approach for CSC.

The feasibility and safety of the brachial artery approach in the treatment of hepatic artery infusion chemotherapy: a retrospective study.

Background: Compared to hepatic artery infusion chemotherapy (HAIC) treatment through the femoral artery (TFA), the brachial artery (TBA) is more flexible and easier for patients to accept. However, the feasibility of TBA has not been studied yet. This study aims to evaluate the feasibility and safety of HAIC via the TBA. Methods: We retrospectively reviewed the medical records of 63 patients with primary liver cancer who were treated with HAIC via TBA. In this study, a total of 163 HAIC procedures were performed via the left brachial artery pathway, and each patient underwent an average of 2.59 procedures. One patient received 5 treatments, 18 patients received 4 treatments, 15 patients received 3 treatments, 12 patients received 2 treatments, and 17 patients received 1 treatment. The main evaluation indicators were the technical success rate and complication rate. Results: The main technical success rate was 99.4% (162/163). No patient required conversion to the femoral artery (TFA) access. All the complications were minor and occurred in 11 patients (6.75%). Subcutaneous ecchymosis occurred in 3 (1.84%) patients, arterial thrombosis in 2 patients (1.23%), and catheter displacement in 6 patients (3.68%). No serious complications occurred. Conclusions: TBA pathway is feasible and safe for HAIC treatment of liver cancer patients. More research is needed in the future to confirm whether TBA is superior to other pathways.

Optimization of Extraction and Separation Process of Notoginsenoside Fc from Panax notoginseng Leaves.

Response surface methodology (RSM) was used to determine the optimal conditions for ultrasound-assisted extraction (UAE) of Notoginsenoside Fc (Fc) from panax notoginseng leaves. The experiment utilized a Box-Behnken design (BBD) and separation conditions were optimized. The optimum extraction conditions were as follows: extraction time = 1.5 h, ethanol concentration = 86%, liquid-to-solid ratio = 19:1. The experimentally obtained values were in accordance with the values predicted by the RSM model. We determined that the RSM model was able to successfully simulate the optimal extraction of Fc from the leaves. Further, Fc was enriched from Panax notoginseng through nine macroporous resins, and HPD-100 macroporous resins were selected for preliminary enrichment of Fc due to its economic costs and benefits. Subsequently, octadecyl silane (ODS) column chromatography was used to improve the purity of Fc to over 90% after separation by ODS column chromatography. Fc with a purity greater than 95% can be obtained by recrystallization. This is the first study that has focused on the extraction and enrichment of Fc from Panax notoginseng leaves using macroporous resin combined with ODS column chromatography, which provides the possibility for further application of Fc.

Protective effect and mechanism of cannabidiol on myocardial injury in exhaustive exercise training mice.

Cannabinoid diphenol (CBD) is a non-toxic main component extracted from cannabis, which has the effects of anti-inflammatory, anti-apoptosis and anti-oxidative stress. In recent years, exercise-induced myocardial injury has become a research hotspot in the field of sports medicine and sports physiology. Exercise-induced myocardial injury is closely related to oxidative stress, inflammatory response and apoptosis. However, there is no clear evidence of the relationship between CBD and exercise-induced myocardial injury. In this study, by establishing an animal model of exhaustive exercise training in mice, the protective effect of CBD on myocardial injury in mice was elaborated, and the possible molecular mechanism was discussed. After CBD intervention, the arrangement and rupture of myocardial fiber tissue and the degree of inflammatory cell infiltration were reduced, the deposition of collagen fibers in myocardial tissue decreased. CBD can also significantly inhibit cardiac hypertrophy. Meanwhile, the expression of IL-6, IL-10, TNF-α, Bax, Caspase-3, Bcl-2, MDA-5, IRE-1α, NOX-2, SOD-1, Keap1, Nrf2, HO-1, NF-κB and COX-2 was recovered to normal. In addition, after CBD intervention, the protein expression of Keap1 was down-regulated, the translocation of Nrf2 from the cytoplasm to the nucleus was significantly increased, then the transcriptional activity was increased, and the expression of the downstream HO-1 antioxidant protein was increased, indicating that CBD may improve the cardiac function of exhaustive exercise training mice by activating Keap1/Nrf2/HO-1 signaling pathway. Molecular docking results also confirmed that CBD had a good binding effect with Keap1/Nrf2/HO-1 signaling pathway proteins. In conclusion, the protective mechanism of CBD on myocardial injury in exhaustive exercise training mice may be to activate Keap1/Nrf2/HO-1 signaling pathway, and then exert anti-inflammatory, anti-apoptosis and inhibition of oxidative stress.

Classification of hepatic cavernous hemangioma or hepatocellular carcinoma using a convolutional neural network model.

Background: Computed tomography (CT) is a common imaging technique for diagnosis of liver tumors. However, the intensity similarity on non-contrast CT images is small, making it difficult for radiologists to visually identify hepatic cavernous hemangioma (HCH) and hepatocellular carcinoma (HCC). Recently, convolutional neural networks (CNN) have been widely used in the study of medical image classification because more discriminative image features can be extracted than the human eye. Therefore, this study focused on developing a CNN model for identifying HCH and HCC. Methods: This study is a retrospective study. A dataset consisting of 774 non-contrast CT images was collected from 50 patients with HCC or HCH, and the ground truth was given by three radiologists based on contrast-enhanced CT. Firstly, the non-contrast CT images dataset were randomly divided into a training set (n=559) and a test set (n=215). Then, we performed preprocessing of the non-contrast CT images using pseudo-color conversion, and the proposed CNN model developed using training set. Finally, the following indicators (accuracy, precision, recall) were used to quantitatively analyze the results. Results: In the test set, the proposed CNN model achieved a high classification accuracy of 84.25%, precision of 81.36%, and recall of 82.18%. Conclusions: The CNN model for identifying HCH and HCC improves the accuracy of diagnosis on non-contrast CT images.

Optimization of AES-128 Encryption Algorithm for Security Layer in ZigBee Networking of Internet of Things.

With the rapid development of network and communication technology, the interaction of various information data is more and more frequent, and people pay more and more attention to information security. The information encryption algorithm is a research hotspot in the field of information security. The Advanced Encryption Standard (AES) algorithm has been widely used in the field of information security with its high security and encryption efficiency. This paper mainly introduces the optimization of the AES-128 encryption algorithm of the security layer in ZigBee networking of the Internet of Things. By analyzing the principles of ZigBee networking and the AES encryption algorithm, the changes are optimized. In this paper, the new S-box cryptographic properties are used after analysis and calculation. The affine transformation period, the number of iteration cycles, and the algebraic expression of the S-box are improved. Its cryptographic properties are better than the S-box of the original algorithm, and the security of the algorithm is improved. In the theory of column hybrid algorithm, the computational complexity is reduced by changing the fixed polynomial, and the efficiency of the column hybrid algorithm is improved. In this paper, the performance of the improved AES algorithm is tested. The results show that, in the power consumption curve experiment, the recovery success rate of the original algorithm is about 42%, and the recovery success rate of the improved algorithm is nearly 60%. The improved algorithm is faster than the original algorithm in achieving a recovery success rate of 100%. Experimental results show that the design can accurately complete the encryption and decryption of the AES algorithm, and the performance is better than the original algorithm, which proves the overall superiority of the algorithm.

Impact of licochalcone A on the progression of diabetic nephropathy in type 2 diabetes mellitus of C57BL/6 mice.

Diabetic nephropathy (DN) is the most common chronic microvascular complication of diabetes. Therefore, it is of great significance to effectively prevent and treat DN. Licochalcone A (LicA) is a flavonoid found in licorice; previous studies have shown that LicA can reduce blood glucose, blood lipids and improve insulin resistance. There has been no research on whether LicA can prevent and treat DN. In this study, an animal model of type 2 diabetes mellitus (T2DM) mice induced by high fat diet/streptozotocin was established, and the intervention of LicA was applied to investigate the protective effect of LicA on the kidneys of DN mice. After 4 weeks of intervention, LicA could effectively reduce blood glucose and alleviate the phenomenon of weight loss in mice. Meanwhile, the levels of MDA, SOD and GSH-Px in the kidney tissue and serum were recovered to different degrees. Besides, LicA decreased the levels of TC, TG and LDL-C in the kidney tissue and increased the level of HDL-C in the kidney tissue. The 24 h urinary protein, blood urea nitrogen (BUN) and serum creatinine (SCr) levels of mice in the treatment group of LicA were significantly lower than those in the model group. Furthermore, HE staining, PAS staining and Masson staining indicated that LicA improved the pathological damage of kidneys, and the kidney index of mice also decreased. Western blotting results indicated that LicA could significantly down-regulate the protein expression of AGEs/RAGE, TGF-ß1, HIF-1α and GLUT1, and up-regulate the protein expression of Nrf2. It provides a theoretical basis for the further development and utilization of LicA.

Organocatalytic Asymmetric Arylation of p-Quinone Phosphonates: A Green Access to Biaryl Monophosphorus Ligands.

Herein, we report a highly efficient organocatalytic asymmetric synthesis of axially chiral biaryl phosphonates with p-quinone phosphonates and 2-naphthols via CPA-catalyzed asymmetric arylations. A series of chiral biaryl monophosphonates were obtained in excellent yields and enantioselectivities (up to 99% yield and 95% ee). This reaction could be operated at a gram scale with a low catalyst loading (0.5 mol %). Remarkably, our approach provides a green and ready access to chiral biaryl monophosphorus ligands. Compound 4ca was successfully converted to novel chiral biaryl monophosphorus ligands 7a, 7b, and 8 with high enantioselectivities in three steps.

Activity Components from Gynostemma pentaphyllum for Preventing Hepatic Fibrosis and of Its Molecular Targets by Network Pharmacology Approach.

Hepatic fibrosis would develop into cirrhosis or cancer without treating. Hence, it is necessary to study the mechanism and prevention methods for hepatic fibrosis. Gynostemma pentaphyllum is a traditional medicinal material with a high medicinal and health value. In this study, nineteen compounds obtained from G. pentaphyllum were qualitative and quantitative by HPLC-FT-ICR MS and HPLC-UV, respectively. Among them, the total content of 19 gypenosides accurately quantified reaches 72.21 mg/g and their anti-proliferation against t-HSC/Cl-6 cells indicated compound 19 performed better activity (IC50: 28.1 ± 2.0 µM) than the other compounds. Further network pharmacology study demonstrated that compound 19 mainly plays an anti-fibrosis role by regulating the EGFR signaling pathway, and the PI3K-Akt signaling pathway. Overall, the verification result indicated that compound 19 appeared to be nontoxic to LO2, was able to modulate the PI3K/Akt signal, led to subG1 cells cycle arrest and the activation of mitochondrial-mediated apoptosis of t-HSC/Cl-6 cells for anti-hepatic fibrosis.

Multiple Roles of Black Raspberry Anthocyanins Protecting against Alcoholic Liver Disease.

This study aimed to investigate the protective effect of black raspberry anthocyanins (BRAs) against acute and subacute alcoholic liver disease (ALD). Network analysis and docking study were carried out to understand the potential mechanism. Thereafter, the serum biochemical parameters and liver indexes were measured, the histopathological changes of the liver were analyzed in vivo. The results showed that all tested parameters were ameliorated after the administration of BRAs with alcohol. Meanwhile, there was increased protein expression of NF-κB and TGF-ß in extracted livers, which was associated with hepatitis and hepatic fibrosis. Furthermore, BRAs and cyanidin-3-O-rutinoside exhibited cytotoxic effects on t-HSC/Cl-6, HepG2, and Hep3B and induced the apoptosis of HepG2 cells; downregulated the protein expression level of Bcl-2; upregulated the level of Bax; and promoted the release of cytochrome C, cleaved caspase-9, cleaved caspase-3, and cleaved PARP in HepG2 cells. In addition, the antioxidant activity of BRAs was tested, and the chemical components were analyzed by FT-ICR MS. The results proved that BRAs exert preventive effect on ALD through the antioxidant and apoptosis pathways.

Hypoglycemic Effects of Licochalcone A on the Streptozotocin-Induced Diabetic Mice and Its Mechanism Study.

Type 2 diabetes mellitus (T2DM) is a type of metabolic illness based on relatively insufficient insulin secretion and insulin resistance (IR) as pathophysiological bases. Currently, it is the main type of diabetes. Hypoglycemic and hypolipidemic effects of licochalcone A (LicA) on high-fat diet and streptozocin-caused T2DM were studied. LicA can remarkably decline the IR index and blood glucose and serum lipid levels. Also, the treatment of LicA can improve the "three more and one less" phenomenon in T2DM mice, such as excessive drinking, eating, urine, and weight loss. In addition, LicA can improve oral glucose tolerance, pancreatic injury, and liver enlargement in T2DM mice. Network pharmacology analysis demonstrated that the observed pharmacological effects were mediated by regulating the insulin signal transduction pathway. Therefore, the PI3K/Akt-signaling pathway was selected for verification; it was demonstrated that LicA could improve the insulin-signaling pathway, protect islet cells, improve IR, reduce blood glucose levels, and alleviate lipid metabolism disorder. Its mechanism of influence may be closely related to LicA up-regulating the liver and pancreas IRS-2/PI3K/AKT-signaling pathway. Among them, the high-dose group of LicA had the best effect, which provided an idea for the use of LicA as a nutritional agent in the cure of T2DM.

Self-expandable metallic stent with 125I seed strand in malignant biliary obstruction: a self-made delivery system and novel implantation method.

BACKGROUND: Malignant obstructive jaundice (MOJ) has a low immediate surgery rate (10-20%) and a poor post-resection survival rate. Although several clinical results have demonstrated the safety and efficacy of stent placement combined with radioactive seeds, the existing implantation methods are time consuming and prone to error. In this study, we introduced a self-made delivery system and novel implantation method for a self-expandable metallic stent (SEMS) with 125I seed strand and evaluated its feasibility and efficacy in MOJ patients. METHODS: Our self-made delivery system was applied to 61 patients (39 males and 22 females, mean age 66.36±10.73 years) from October 2018 to June 2020 in our center with a novel implantation method. The preparation and manipulation processes were described in detail. Technical and clinical successes were recorded, and stent patency and overall survival (OS) were assessed. A P value of less than 0.05 indicated a significant difference. RESULTS: Stents with 125I seed strands were successfully placed in all 61 participants with our novel implantation method. The clinical success rate was 96.7%, and no severe procedure-related complications were found except bile leakage through puncture in 1 participant. The median duration of primary stent patency was 120 (37, 233.5) days, and the median OS was 169 (41, 270) days. CONCLUSIONS: Our self-made delivery system with a novel SEMS implantation method with 125I seed strand was feasible and effective for MOJ patients and significantly simplified the current implantation approach.

Design, Synthesis, and Resolution of Spirocyclic Bisoxindole-Based C2-Symmetric Diols.

A new type of spirocyclic bisoxindole-based C2-symmetric diols (SBIDOLs) was designed and synthesized. A series of racemic SBIDOL derivatives (6a-6g) were readily synthesized from commercially available 2-halo-5-methoxyanilines 1 (X = Cl or Br) through N-mono alkylation, acylation, oxidation, double intramolecular Friedel-Crafts reaction, and demethylation reactions. The optical resolution of racemic 6b was achieved via fractional crystallization of their bis-l-menthoxycarboxylates. Further modifications of SBIDOLs were investigated, leading to 5,5'-diaryl SBIDOL derivatives (11a and 11b) through Pd-catalyzed Suzuki coupling and DM-SBIDOL 12 by Pd/C-catalyzed hydrogenative dechlorination reactions.

Ruthenium-Catalyzed Highly Enantioselective Synthesis of cis-3-Quinuclidinols via DKR Asymmetric Transfer Hydrogenation.

A method for the enantioselective synthesis of cis-3-quinuclidinols by Ru-catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution is described. The reaction proceeded under mild conditions using ammonium formate as the hydrogen donor, affording the products in high yields (up to 99%) with excellent diastereoselectivity (up to 99:1 dr) and enantioselectivity (95-99% ee). This protocol was applicable to gram-scale preparation with perfect enantioselectivity through simple recrystallization.