Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A-E (1-5), and three lanostanoids, ganothenoids F-H (6-8), along with 24 known ones (9-32), were isolated from the fruiting bodies of Ganodrma theaecolum. The structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1-32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L^-1, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L^-1. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.
Humans ; Fruiting Bodies, Fungal/chemistry* ; Triterpenes/isolation & purification* ; Neuroprotective Agents/isolation & purification* ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism* ; Ganoderma/chemistry* ; Apoptosis/drug effects* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/drug effects* ; Hydrogen Peroxide/toxicity* ; Molecular Docking Simulation

With the rapid development and expansion of the scale of the industry of Chinese materia medica,a large number of by-products in the process industrialization of Chinese materia medica have been produced,among which,the solid by-products of Chinese materia medica have been favoured by researchers due to the fact that they are rich in a large number of proteins,cellulose,hemicellulose,lignin,etc.,which can be used in the preparation of high value-added products.Therefore,the authors elaborated on the research on biochemical conversion,thermochemical conversion,resource oriented chemical components,preparation of biomass fuel,new composite materials and high-efficiency adsorbent of solid by-products in the process of industrialization of Chinese materia medica in recent years,aiming to provide theoretical basis for the comprehensive and high-value utilization of the solid by-products of Chinese materia medica and extension of the industrial chain.

ObjectiveTo observe the clinical effect of Qingxin Zishen decoction on hot flashes after endocrine therapy for prostate cancer and explore its therapeutic mechanism. MethodA total of 60 patients who met the criteria and were admitted to Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 were collected and randomly divided into a treatment group and a control group， with 30 cases in each group. The treatment group was treated with Qingxin Zishen decoction， while the control group was only given routine nursing. The observation period of this study was eight weeks. The improvement of hot flash frequency， hot flash degree， hot flash score， ISS score， and TCM syndrome score were observed in the two groups before and after treatment. The changes of serum endothelin-1 （ET-1）， nitric oxide （NO）， calcitonin gene-related peptide （CGRP）， prostate specific antigen （PSA）， and testosterone were detected. ResultIn terms of efficacy， after treatment， the frequency， degree， and score of hot flashes， ISS score， and TCM syndrome score decreased in the treatment group （P<0.05）. Compared with the control group， all indicators were better in the treatment group （P<0.05）. In terms of laboratory indicators， after treatment， the serum NO level in the treatment group was increased. ET-1 level was decreased. The ratio of ET-1/NO was decreased， and the CGRP level was decreased （P<0.05）. However， testosterone and PSA levels were not significantly changed . Compared with the control group， after treatment， the serum NO level in the treatment group was higher， and the level of ET-1 was lower. The ratio of ET-1/NO and the CGRP level were lower （P<0.05）. There were no significant differences in testosterone and PSA levels between the two groups. ConclusionQingxin Zishen decoction can significantly improve hot flashes in patients with prostate cancer after endocrine therapy. The mechanism of Qingxin Zishen decoction may be to improve the vasomotor function by regulating the expression level of vasomotor factors， so as to treat hot flashes.

Objective:To explore the expression of endosialin, i.e., CD248 in human hypertrophic scars (HSs) and its regulatory effect on the phenotype of hypertrophic scar fibroblasts (HSFs).Methods:The method of experimental research was used. From March to May, 2023, 3 pediatric patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 2 females and 1 male, aged one year ten months to two years. The HS tissue resected during the surgery and the remaining full-thickness skin graft, i.e., normal skin tissue after full-thickness skin grafting were collected from the aforementioned pediatric patients for subsequent experiments. Using the aforementioned two types of tissue, the histological structures were observed by hematoxylin-eosin staining, collagen distribution was observed by Masson staining, and the expression of CD248 was observed and measured by immunohistochemical staining. The primary HSFs were isolated from HS tissue using explant culture technique, and the 3 rd to 5 th passages of HSFs were used in subsequent experiments. According to the random number table, HSFs were divided into immunoglobulin G78 (IgG78)-treated group and IgG control group, which were treated with 200 nmol/L human CD248 monoclonal antibody IgG78 and human IgG control antibody for 24 h, respectively. The mRNA expressions of collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) in HSFs were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction, the protein expressions of Col Ⅰ and α-SMA in HSFs were detected by Western blotting, and the intracellular location and protein expressions of Col Ⅰ and α-SMA were detected by immunofluorescence method. The number of samples in each experiment was 3. Data were statistically analyzed with paired sample t test and independent sample t test. Results:Compared with those in normal skin tissue, the epidermis and dermis in HS tissue were significantly thicker, with massive accumulation and disordered arrangement of collagen in the dermis. The expression of CD248 in HS tissue was significantly upregulated compared with that in normal skin tissue ( t=5.29, P<0.05). At post treatment hour 24, the mRNA expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.39±0.05 and 0.56±0.09, respectively, which were significantly lower than 1.00±0.07 and 1.00±0.08 in IgG control group, respectively (with t values of 11.87 and 6.49, respectively, P values all <0.05). The protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.617±0.011 and 0.67±0.14, respectively, which were significantly lower than 1.259±0.052 and 1.23±0.16 in IgG control group, respectively (with t values of 20.92 and 4.52, respectively, P values all <0.05). At post treatment hour 24, immunofluorescence staining showed that Col Ⅰ and α-SMA mainly located in the cytoplasm of HSFs in the two groups, and the protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were obviously downregulated compared with those in IgG control group. Conclusions:The expression of CD248 is significantly upregulated in human HS. Targeted blockade of CD248 can significantly inhibit the collagen synthesis by HSFs and the transdifferentiation of HSFs into myofibroblasts.

Objective To investigate the changes in serum levels of angiopoietin-like protein 4(ANGPTL4)and ubiquitin carboxyl terminal hydrolase-1(UCH-L1),and CHA2DS2-VASc score in patients with non-valvular atrial fibrillation(NVAF)and acute cerebral infarction(ACI),and their diagnostic value.Methods A total of 162 NVAF patients treated in our hospital from Janu-ary 2021 to January 2023 were enrolled and divided into a combined group(45 cases)and a non-combined group(117 cases)according to having ACI or not.General clinical information,CHA2DS2-VASc scores,and serum levels of ANGPTL4 and UCH-L1 were collected and detected.Spearman correlation analysis was applied to evaluate the correlation of ANGPTL4,UCH-L1 and CHA2DS2-VASc score.Multivariate logistic regression analysis was performed to identify the in-fluencing factors of NVAF combined with ACI.ROC curve was plotted to evaluate the diagnostic value of serum ANGPTL4,UCH-L1,and CHA2DS2-VASc score for NVAF combined with ACI.Results The ANGPTL4 level was significantly lower,and the UCH-L1 level and CHA2DS2-VASc score were obviously higher in the combined group than the non-combined group(P＜0.05).In the patients with NVAF combined with ACI,serum ANGPTL4(r=-0.548,P＜0.05)and UCH-L1(r=0.400,P＜0.05)levels were negatively and positively correlated with CHA2DS2-VASc score,respectively.ANGPTL4,UCH-L1 and CHA2DS2-VASc were the risk fac-tors for ACI in NVAF patients(P＜0.05,P＜0.01).The AUC value of combined serum ANGPTL4 and UCH-L1 levels and CHA2DS2-VASc score for diagnosing NVAF complicated with ACI was 0.926(95％CI:0.874-0.961).Conclusion Combined detection of serum AUCH-L1 and NGPTL4 levels and CHA2DS2-VASc score can significantly improve the diagnostic value of NVAF patients with ACI.

In order to overcome the difficulty in lung parenchymal segmentation due to the factors such as lung disease and bronchial interference, a segmentation algorithm for three-dimensional lung parenchymal is presented based on the integration of surfacelet transform and pulse coupled neural network (PCNN). First, the three-dimensional computed tomography of lungs is decomposed into surfacelet transform domain to obtain multi-scale and multi-directional sub-band information. The edge features are then enhanced by filtering sub-band coefficients using local modified Laplacian operator. Second, surfacelet inverse transform is implemented and the reconstructed image is fed back to the input of PCNN. Finally, iteration process of the PCNN is carried out to obtain final segmentation result. The proposed algorithm is validated on the samples of public dataset. The experimental results demonstrate that the proposed algorithm has superior performance over that of the three-dimensional surfacelet transform edge detection algorithm, the three-dimensional region growing algorithm, and the three-dimensional U-NET algorithm. It can effectively suppress the interference coming from lung lesions and bronchial, and obtain a complete structure of lung parenchyma.
Algorithms ; Neural Networks, Computer ; Tomography, X-Ray Computed

Objective To investigate the heterogeneity of immunomodulatory function of exosomes secreted from human umbilical cord-derived mesenchymal stem cells(hUC-MSC).Methods Five different hUC-MSCs lines were isolated and cultured.Exosomes were isolated from the supernatant.The expression of specific surface markers CD9,CD63,CD81 and CD44 was detected by flow cytometry.The protein concentration of hUC-MSCs exosomes(hUC-MSCs-ex)was evaluated by the BCA assay.Concanavalin A and rhIL-2 stimulated umbilical cord blood mononuclear cells (UBMCs) from healthy donor were co-cultured at different concentrations of hUC-MSCs-ex from different cell lines for 72 h.The growth rate of UBMCs was detected by MTT assay.ELISA was used to test the levels of IFN-γ and TNF-α of the supernatants.The UBMCs co-cultured with hUC-MSCs were co-cultured with K562 cells at the ratio of 5∶1.The cytotoxic activity was calculated by MTT assay.Results hUC-MSCs-ex expressed CD9,CD63,CD81and CD44.Different hUC-MSCs lines had different regulating activities on the proliferation,secretion and killing ability of UBMCs.Conclusion hUC-MSCs-ex has heterogeneity of immunomodulatory function on UBMCs.

Objective To investigate the feasibility and effectiveness of focused ultrasound on the acne of rabbit ear.Methods Eighteen male rabbits were randomly divided into blank control group,model control group and ultrasound irradiation group.Acne rabbit ear model was established by Kligman's method in model control group and ultrasound irradiation group.Then,continuous ultrasonic irradiation was given in ultrasound irradiation group.Pathological changes were observed at the time of before and after ultrasound irradiation and 14 days after ultrasound irradiation.Results After modeling,hair follicle expansion,hyperkeratosis,acupoint hypertrophy were observed in blank control group.Compared with blank control group,the thickness of horn layer,the sebaceous gland diameter and other index in model controlgroup were statistically significant (P＜0.01);After irradiation,there were hyperemia and edema in epidermis,angiotelectasis and inflammatory infiltrating,but coagulative necrosis in slice was not observed,14 days later,hair follicle mild expansion,mild keratosis,spiny thinning were observed in ultrasound irradiation group,when compared with model control group,the thickness of horn layer,sebaceous gland diameter and other index were decreased in ultrasound irradiation group,and the differences were statistically significant(P＜0.01).Conclusion The ultrasonic focusing treatment on rabbit ear acne is feasible and effective.

Objective To introduce a improved method for the production of hemoglobin liquid by use of the hemoglobin electro‐phoresis alkaline .Methods First ,we used the pipette to absorb the settlement of red blood cells from a batch of EDTA anticoagula‐ted whole blood specimens ,then dropped them into the 0 .9% saline washed human erythrocytes .With the help of the pipette nozzle we pipet from the liquid surface to bottom repeatedly ,made the red cells suspended in the liquid evenly .The samples should be cen‐trifuged and the red blood cells fully deposited at the bottom ,then poured the supernatant after centrifugation to remove the impuri‐ties in plasma and leave the allowance of red blood cells .We add distilled water or hemolysin to lysis RBC .Hands up test tubes rack using wrist gently back and forth several times until the hemolysis was clear and transparent .Results Compared the results of the modified method and the traditional method ,then the two results compared with the results of HPLC recommended by international association of thalassemia method .Compared the results of three screening methods with that of the thalassemia gene identification method .So we could objectively evaluate the reliability of the test .Conclusion The result of the improved method are same to the electrophoretogram by SOP operation ,it will be more efficient and reduce the cost of reagent .The whole process of preparing hemo‐globin solution doesn′t contact with any chemical reagent .So there will be no pollution to the environment ,and it also reduces the harmful of toxic reagent to the human body .