BACKGROUND:Bismth-doped iron nanoparticles modified by hyaluronic acid (HA-BiIOPs) not only act as an effective MRI contrast agent, but also as a radiotherapy sensitizer.OBJECTIVE:To fabricate the HA-BiIOPs and to observe its effect to enhance the radiosensitivity of glioblastoma cells U87MG under X-ray radiation.METHODS:HA-BiIOPs were synthesized using hydrothermal polyol method. (1) Cytotoxicity: A cytotoxicity test was carried out on U87MG cells and rat vascular smooth muscle cells (VSMCs). Cell proliferation rate of two kinds of cells cultured with different concentrations of HA-BiIOPs (0, 12.5, 25, 50, 100, 200, 400 mg/L) at 24 hours after culture were determined by cell counting kit-8 assay. (2) Histological analysis: ICR mice were sacrificed after intravenous injection of HA-BiIOPs, and pathological changes of mouse visceral organs were observed under an optical microscope. (3) Cellular uptake: The HA-BiIOPs after entered into the cytoplasm were observed by Prussian blue staining. (4) Radiosensitization test: U87MG cells at Logarithmic growth stage were cultured in culture medium as control group, subjected to X-ray irradiation (0, 3, 6, 9 Gy) as radiotherapy group, cultured in HA-BiIOPs (0, 12.5, 25, 50, 100, 200 and 400 mg/L) as HA-BiIOPs group or subjected to HA-BiIOPs culture plus X-ray irradiation as combined therapy group. Then, the cell proliferation rate and cloning efficiency were measured at 24 hours after treatment.RESULTS AND CONCLUSION:(1) The HA-BiIOPs at different concentrations were non-cytotoxic for VSMC and U87MG cells. (2) After intravenous injection of HA-BiIOPs, there was no obvious toxicity to the mouse susceptible organs. (3) After 6 hours of culture, the HA-BiIOPs could be internalized by U87MG cells. (4) The proliferation rate of U87 cells was negatively correlated with the concentration of HA-BiIOPs (0-200 mg/L) and X-ray dose (0-9 Gy). Especialy, the combination of 6 Gy X-ray irradiation with 200 mg/L HA-BiIOPs dramatically decreased the cell viability that was decreased to (41±7)%. In the combined therapy group with 6 Gy X-ray and 100 mg/L HA-BiIOPs, the cells proliferation rate was significantly lower than that in the control and radiotherapy groups (P < 0.05). These results indicate that HA-BiIOPs have a radiosensitizative effect on glioblastoma cells U87MG.

Objective To investigate the optimal gamma passing rate of intensity-modulated radiotherapy (IMRT) dosimetric verification in the treatment of esophageal cancer using a three-dimensional dose verification system EDoseTM.Methods Twenty five esophageal cancer patients treated by 7-field IMRT were retrospectively reviewed.Measured dose distribution were reconstructed on CT image and evaluated by gamma analysis and DVH metrics using the EDoseTM system.Plans with DVH metrics dose difference ＜ 5％ or with gamma passing ＞ 90％ under 3％/3 mm criteria were accepted.The optimal gamma passing rate for criteria of 5％/3 mm,3％/3 mm,2％/2 mm were investigated by drawing the receiver operating characteristic (ROC) curves and calculating the Youden Index.The sensitivity and specificity of the these optimal thresholds in the plan verification were also analyzed.Results The optimal thresholds for global gamma indices with 5％/3 mm,3％/3 mm,2％/2 mm were 98.66％,94.84％,78.56％,respectively.In the 90％ common threshold,The sensitivity and specificity for common 90％ threshold and optimal threshold under 3％/3 mm criteria were 0.17 vs.0.85 and t 0.84 vs.0.27,respectively.The sensitivity and specificity were 0.89,0.65 and 0.23,0.47 for optimal thresholds under 5％/3 mm and 2％/2 mm criteria,respectively.Conclusions The sensitivity of optimal threshold gamma passing rate improved significantly compared with the common threshold (90％) at 3％/3 mm criteria.,The sensitivity and the specificity were more balanced at the 2％/2 mm criteria compared with those at 3％/3 mm criteria.

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.
Humans ; Shock, Septic/therapy* ; Exosomes/metabolism* ; Sepsis/therapy* ; Extracellular Vesicles/metabolism* ; RNA/metabolism*

Objective:To examine the structural network changes in participants with amnestic mild cognitive impairment(aMCI)and investigate the correlation between these changes and the onset of Alzheimer's disease(AD).Methods:In this prospective study, a total of 100 individuals with amnestic mild cognitive impairment(aMCI)were enrolled as the research group.Additionally, 25 healthy individuals who were matched in terms of age and sex were enrolled as healthy controls.Upon enrollment, all participants underwent MRI scans, neuropsychological assessments, and clinical evaluations.The participants were then followed every 6 months for a period of 36 months or until they withdrew from the study.Based on the outcome of the follow-up(whether Alzheimer's disease occurred), the aMCI participants were divided into two groups: stable aMCI group and progressive aMCI group.The Chinese version of the Brief Mental State Examination(MMSE), the Montreal Cognitive Assessment(MoCA), the Clinical Dementia Rating Scale(CDR), and the Auditory Word Learning Test(AVLT)were utilized to evaluate the overall mental and cognitive status of the subjects.Pearson correlation analysis was employed to investigate the relationship between structural network changes and cognitive decline.Logistic regression was performed to analyze the predictive ability of structural network changes in determining the onset of AD.Results:Compared to the stable aMCI group, the progressive aMCI group exhibited lower levels of global efficiency( P=0.002), local efficiency( P=0.007), feeder connections( P=0.003), local connections( P=0.008), and right precuneus nodal efficiency( P=0.010).Correlation analysis revealed that global efficiency( r=0.604, P=0.002), feeder connections( r=0.513, P=0.012), and right precuneus nodal efficiency( r=0.504, P=0.014)were correlated with AVLT-delay scores(baseline)in the progressive aMCI group.A logistic regression model demonstrated that global efficiency, feeder connections, and right precuneus nodal efficiency could significantly predict the onset of AD(all P<0.05, AUCunited=0.797, 95% CI: 0.684-0.884, sensitivity=73.91, 95% CI: 51.6-89.8, specificity=76.60, 95% CI: 62.0-87.7). Conclusions:Among participants with aMCI, individuals who exhibit lower global efficiency, feeder connections, or right precuneus nodal efficiency are at a higher risk of developing AD.These indicators are anticipated to serve as new targets for clinical intervention.

Objective:To investigate the factors influencing recipient liver regeneration after full-size split liver transplantation (fSLT).Methods:The clinical data of patients undergoing split liver transplantation in the Affiliated Li Huili Hospital of Ningbo University from May 2019 to Sep 2023 were retrospectively collected. Graft volume (GV) and initial graft volume (IGV) at (30±7) days after operation were measured, and postoperative liver regeneration rate (LRR) was calculated. The patients undergoing fSLT were divided into high regeneration group and low regeneration group with LRR=30% as boundary. The differences of donor and recipient data and perioperative data between the two groups were compared.Results:A total of 52 patients were included. The low fSLT regeneration group (16 cases) was compared with the high fSLT regeneration group (36 cases), and in high fSLT regeneration group donor age was lower, the donor liver steatosis was less, GRWR was lower, the incidence of hepatitis B virus-related liver disease was lower, the postoperative diagnosis of malignant liver disease was lower, the intraoperative blood loss was less, and the postoperative platelet count was higher. The levels of liver enzyme and total bilirubin (TBiL) were higher than those in high regeneration group ( P<0.05). Conclusions:Donor age, donor liver steatosis, GRWR, hepatitis B virus associated liver disease, and recipient pathogenesis are important factors affecting liver regeneration after fSLT. Postoperative platelet and liver enzyme levels are important indicators for monitoring liver regeneration after fSLT.

Objective:To analyze the genetic evolution and molecular characteristics of H5N8 avian influenza viruses (AIVs) isolated from the poultry in a live poultry market (LPM) in Urumqi, Xinjiang.Methods:Oropharyngeal and cloacal swabs of poultry were collected from a LPM in Urumqi in 2016. AIVs were isolated by inoculating swab samples into chicken embryos. Hemagglutination test and RT-PCR were used to identify the AIVs. The genes of isolated AIVs were amplified with the universal primers of AIV and whole-genome sequencing was also performed. Pairwise sequence alignment and analysis of phylogenetic and molecular characteristics were performed using BLAST, Clustal W, MEGA-X and DNAStar software.Results:Five H5N8 AIVs were isolated from poultry. These strains shared a nucleotide identity of 99.70%-100.00%, which indicated that they were from the same source, and were named XJ-H5N8/2016. Phylogenetic analysis based on hemagglutinin( HA), NS and PB2 genes showed that these isolates were clustered together with H5N8 AIVs isolated from the migratory swans in Hubei, Shanxi and Sanmenxia, and the ducks in India during 2016 to 2017. Moreover, they were also clustered together with H5N6 AIVs isolated from minks in China and the first case of human infection in Fujian. The phylogenetic tree of neuraminidase( NA) gene indicated the five isolates clustered together with H5N8 AIVs isolated from ducks in India in 2016, and the phylogenetic trees of PB1, MP, PA and NP genes showed that they were clustered together with H5N8 AIVs isolated from wild birds and poultry in Egypt, Cameroon, Uganda, Congo and other African countries in 2017. The HA cleavage sites of XJ-H5N8/2016 contained five consecutive basic amino acids, indicating high pathogenicity. Multiple mutations in the genes of XJ-H5N8/2016 could enhance its virulence and pathogenicity to mammals. Conclusions:The five strains of H5N8 AIVs isolated from the LPM were highly pathogenic and closely related to the H5N8 AIVs isolated from migratory birds and poultry in Hubei, Shanxi, Sanmenxia area, Africa and India during 2016 to 2017. Meanwhile, some of the viral genes were also closely related to the H5N6 AIVs isolated from the minks and human in China. Multiple mutations could increase the virulence and pathogenicity of AIVs to mammals, which could pose a potential threat to public health.