Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Five compounds were isolated and purified from the water extract of Elaeagnus oxycarpa Schlechtend leaf by multi-dimensional reversed-phase preparative liquid chromatographic system based on the separation and enrichment model. Their structures were identified by spectral analysis such as NMR, MS, UV, IR and by comparison with literature information as 2,4(1H,3H)-pyrimidinedione (1), elaeagnussugarester B (2), elaeagnussugarester A (3), elaeagnussugarester C (4), gallic acid (5). Compounds 2-4 are new compounds, compound 1 was isolated from Elaeagnus oxycarpa Schlechtend for the first time. The antioxidant and anti-tyrosinase activities of these compounds were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical method, the potassium ferricyanide reduction method and the colorimetric method with L-tyrosine as substrate. The results showed that compounds 2-5 have good antioxidant activities and inhibitory effect on tyrosinase. Compound 4 exhibited the most strong antioxidant activities, with IC₅₀ = 3.59 ± 0.06 μmol·L^-1 for DPPH free radical scavenging ability, IC₅₀ = 10.04 ± 0.20 μmol·L^-1 for ABTS free radical scavenging ability, and total reduction capacity of compound 4 was better than vitamin C respectively. Compound 3 possessed better inhibitory effect on tyrosinase with IC₅₀ = 0.25 ± 0.06 mmol·L^-1.

Dipsaci Radix is a commonly used Chinese herbal medicine in China, with triterpenoid saponins as the main active components. β-Amyrin synthase, a member of the oxidosqualene cyclase superfamily, plays a crucial role in the biosynthesis of oleanane-type triterpenoid saponins. Asperosaponin Ⅵ is an oleanane-type triterpenoid saponin. To explore the β-amyrin synthase genes involved in the biosynthesis of asperosaponin Ⅵ in Dipsacus asper, this study screened the candidate genes from the transcriptome data of D. asper. Two β-amyrin synthase genes, Da OSC1 and Da OSC2, were identified by phylogenetic analysis and correlation analysis. The coding sequences of Da OSC1 and Da OSC2 were 2 286 bp and 2 295 bp in length, encoding 761 and 764 amino acids,respectively. Multiple sequence alignments showed that Da OSC1 and Da OSC2 had three conserved motifs( DCTAE, QW, and MWCYCR) unique to the oxidosqualene cyclase family. Real-time quantitative PCR results showed that Da OSC1 and Da OSC2 had the highest expression levels in the roots. Compared with normal growth conditions, the low-temperature treatment significantly upregulated the expression of Da OSC1 and Da OSC2. Agrobacterium-mediated transient expression of Da OSC1 and Da OSC2 in Nicotiana benthamiana resulted in the production of β-amyrin, which suggested that Da OSC1 and Da OSC2 were able to catalyze the synthesis of β-amyrin. This study clarified the catalytic functions of two β-amyrin synthases in D. asper, analyzed their expression patterns in different tissue and at low temperatures. The findings provide a foundation for further studying the biosynthetic pathway and regulatory mechanism of asperosaponin Ⅵ in D. asper.
Intramolecular Transferases/chemistry* ; Phylogeny ; Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Dipsacaceae/classification* ; Saponins/metabolism* ; Oleanolic Acid/metabolism*

OBJECTIVE: To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells. METHODS: K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC₅₀ were calculated separately for each drug. Based on the value of IC₅₀ of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy. RESULTS: Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(r =-0.991， r =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( P <0.05). The proportion of K562 cells in the G₀/G₁ phase was significantly increased with the combined treatment of two drugs( P <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins. CONCLUSION The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.
Humans ; Ginsenosides/pharmacology* ; Imatinib Mesylate ; K562 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction/drug effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Drug Synergism ; Apoptosis/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Proliferation/drug effects*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P＜0.00001],24hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P＜0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasma β-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.

Objective To investigate the association between D-dimer levels within 2 hours of admission and in-hospital major adverse events (MAEs) in patients with acute type A aortic dissection (ATAAD) who underwent total arch replacement combined with frozen elephant trunk (FET) implantation. Methods This retrospective study included patients with ATAAD who underwent total arch replacement with FET implantation at Fuwai Yunnan Cardiovascular Hospital from September 2017 to December 2022. Patients were divided into two groups based on the occurrence of in-hospital MAEs: a MAEs group and a non-MAEs group (control). Perioperative data were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify risk factors for in-hospital MAEs, which included in-hospital death, gastrointestinal bleeding, paraplegia, acute kidney injury, low cardiac output syndrome, stroke, respiratory failure, multiple organ dysfunction syndrome, and severe infection. The predictive value of D-dimer was evaluated using the area under the receiver operating characteristic curve (AUC). Results A total of 218 patients were included (157 males, 61 females), with a mean age of (51.54±9.79) years. There were 152 patients in the non-MAEs group and 66 in the MAEs group. The overall incidence of in-hospital MAEs was 30.3%, and the in-hospital mortality rate was 2.8% (6/218). Compared to the non-MAEs group, the MAEs group had significantly higher levels of D-dimer and lactate, as well as longer cardiopulmonary bypass time, aortic cross-clamp time, and ICU length of stay (all P<0.05). Multivariate logistic regression analysis identified D-dimer as an independent risk factor for in-hospital MAEs [OR=1.077, 95%CI (1.020, 1.137), P=0.013]. The AUC for the D-dimer level within 2 hours of admission to predict in-hospital MAEs was 0.83 [95%CI (0.736, 0.870), P<0.001]. The optimal cutoff value was 2.2 μg/mL, with a sensitivity of 84.8% and a specificity of 73.0%. Conclusion The serum D-dimer level is an independent risk factor for in-hospital MAEs in patients with ATAAD following total arch replacement with FET implantation. D-dimer levels on admission can help clinicians optimize risk stratification and perioperative management, potentially reducing the incidence of early adverse events.

Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using Acanthopanax senticosus herbal residues as raw material and KOH as activating agent through a one-step pyrolysis method. The prepared carbon-based material was systematically characterized by powder X-ray diffraction, scanning electron microscopy, N₂ adsorption-desorption and Fourier-transform infrared spectroscopy. The results show that the three-dimensional ordered porous carbon materials prepared with KOH as the activator via pyrolysis possess abundant functional groups, high porosity, and high specific surface area, with a specific surface area of 1 471.6 m²·g^-1. The three-dimensional ordered porous carbon materials prepared at 800 ℃ exhibits a high drug loading capacity (78.0%) and drug release rate (86.8%) for 5-fluorouracil. Three-dimensional orderly porous carbon materials show significant application advantages in drug construction, and their high specific surface area and adjustable pore size structure significantly improve the drug load rate and drug release rate, providing a solid foundation for the development of efficient and accurate drug delivery system.