PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53％.Cardiovascular and cerebrovascular diseases(36.67％)and nervous system diseases(23.33％)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90％donations,and the others were from outside the city.The postmortem delay time was relatively short,90％within 12 hours and 10％more than 12 hours.69.23％of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40％donated brains.The comorbidity rate of samples over 80 years old was 100％.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

The epidemic caused by coronavirus poses a serious threat to human health, but there is no specific drug or vaccine for the treatment of this kind of virus infection. Herein, this article selects typical case studies in recent years and reviews the medicinal chemistry strategies of anti-SARS-CoV, MERS-CoV and other coronavirus drugs from the perspective of medicinal chemistry, and tries to provide some clues to current drug research againstSARS-CoV-2.

Objective To evaluate the anti-diabetic effect and mechanism of a novel G protein coupled receptor 40 (GPR40) agonist SZZ15 -11. Methods Transactivation assay based on luciferase reporter gene was performed to explore the agonist activity of the compounds to GPR40. The primary mouse islets were used to evaluate the insulinotropic ability of the compounds. After oral administration of the tested compounds once,the plasma concentrations of glucose,insulin and glucagon like peptide 1 (GLP-1) were determined in normal mice followed oral glucose loading. The effect of the compounds on gastric emptying was also evaluated in normal mice given orally once. In spontaneous type 2 diabetic KKAy mice orally administrated compound for one month,the plasma glucose concentration were measured. Results The compound SZZ15 -11 activated GPR40 with EC50 of 1. 2 μmol·L-1. It significantly promoted glucose-stimulated insulin secretion (GSIS) in mouse primary islets by 61. 1％ (P < 0. 05) under high glucose conditions (16. 8 mmol·L-1). Oral administration of SZZ15-11 (50 mg·kg-1) once decreased the plasma concentrations of glucose in normal ICR mice followed oral glucose loading,reduced the area under the curve (AUC) by 13. 1％ (P < 0. 05) ,and increased insulin secretion after oral glucose load by 46. 6％ (P < 0. 05). SZZ15-11 also obviously delayed the gastric emptying rate in normal mice at a dose of 50 mg·kg-1,which reduced the area of the serum acetaminophen concentration-time curve (P <0. 05). At two doses of 50 and 100 mg·kg-1,plasma GLP -1 levels in normal mice after oral glucose load was increased (P <0. 05). In the type 2 diabetic KKAy mice administrated with SZZ15 -11 at the dose of 50 and 100 mg·kg-1 for 4 weeks,the fasting blood glucose was decreased significantly decreased (P < 0. 01 and P < 0. 05). Conclusion The novel GPR40 agonist SZZ15 -11 promoted glucose-dependent insulin and GLP-1 secretion,thus ameliorated glucose metabolism in type 2 diabetic mice. It will be a potential anti-diabetic compound candidate which is worth of further exploration.

OBJECTIVE: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes. METHODS: The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes. RESULTS: The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%. CONCLUSION The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.
Chromatography, High Pressure Liquid ; Liposomes ; Magnetic Resonance Spectroscopy ; Taxoids

OBJECTIVE: To evaluate and to compare dimensional alterations of hard and soft tissues in molar extraction sites with irregular deficiency of bone plates due to advanced periodontitis receiving two different procedures, namely the flapped and flapless techniques with Bio-Gide membrane covering the Bio-Oss material for ridge preservation. METHODS: Twenty-three patients with 24 infected-molar extraction sites received ridge preservation procedure, the first consecutive 12 sites belonged to the flap group (a full thickness mucoperiosteal flap and primary soft tissue closure) and the following 12 sites belonged to the flapless group (minimal flap with a collagen sponge and a secondary soft tissue closure). Width of keratinized tissue was evaluated before tooth extraction and after 6-month healing. Parallel periapical radiographs were taken immediately and 6 months after extraction to evaluate vertical bone changes. The width of the ridge was measured in the center of the ridge at the time of tooth extraction and after 6 months at implant placement. RESULTS: After 6 months, width of keratinized tissue decreased (1.6±1.5) mm in the flap group (P=0.004) when compared with (0.3±1.6) mm in the flapless group (P>0.05). Both groups showed increases in ridge height from the central aspect, (5.53±4.20) mm for flap group and (7.70±4.35) mm for flapless group. These differences between the groups were not statistically significant (P=0.226). The ridge widths were (9.5±2.2) mm for flap group and (9.3±1.0) mm for flapless group at the time of implant insertion, and no statistical significance was observed between the flap and flapless groups. CONCLUSION The study points out that both ridge preservation techniques were effective in increasing ridge height and minimizing ridge resorption after tooth extraction, and the ridge width allowed the placement of implants 6 months after ridge preservation. The flapless technique gave positive outcome in terms of the keratinized gingival width than that of the flap technique.
Alveolar Process ; Humans ; Molar ; Periodontitis ; Tooth Extraction ; Tooth Socket

Objective:To study the feasibility of a new composite mineralized collagen membrane in alveolar ridge preservation.Methods:The third mandibular premolars on both sides were extracted from 12 dogs,the 24 alveolar sockets were randomly assigned into A,B and C groups(n =8).The distal alveolar sockets of group A was immediately implanted with the new composite mineralized collagen membrane and bone graft material,those of group B with bone graft material,group C was the blank control.The healing of sockets was evaluated by gross observation,morphological measurements,X-ray microscope and photographs of spiral CT.Results:The horizontal width of the alveolar process of group A was bigger than that of group B (P ＜ 0.05),that of group B was bigger than that of group C (P ＜ 0.05).The region of extraction interest in spiral CT value was higher in group A than that in group B and C (P ＜ 0.05).The extraction sockets were generated new bone and the degree of reconstruction measurements was higher in group A than that in group B and C (P ＜ 0.05).Conclusion:The new composite mineralized collagen membrane can induce the regeneration of new bone,and preserve the alveolar.