简介：AbstractBackground:High-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student’s t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch’s ANOVA test followed by Holm-Sidak’s multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t= 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P < 0.001) and heat shock protein 70 (HSP70) (0.03 ± 0.01 vs. 0.46 ± 0.09 vs. and 0.42 ± 0.07, F= 64.490, P < 0.001) were significantly different between the untreated, IRE and H-FIRE zones, but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone (both P > 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C vs. 16.20 ± 7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

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简介：AbstractBackground:Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.Methods:The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD.Results:A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05).Conclusion:Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.

简介：AbstractBackground:The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly, with confirmed cases distributed across 31 counties. However, the epidemiology of brucellosis transmission has not been fully elucidated. To characterize the infecting strains isolated from humans, multiple-locus variable-number tandem repeats analysis (MLVA) and whole-genome single-nucleotide polymorphism (SNP)-based approaches were employed.Methods:Strains were isolated from two males blood cultures that were confirmed Brucella melitensis positive following biotyping and MLVA. Genomic DNA was extracted from these two strains, and whole-genome sequencing was performed. Next, SNP-based phylogenetic analysis was performed to compare the two strains to 94 B. melitensis strains (complete genome and draft genome) retrieved from online databases.Results:The two Brucella isolates were identified as B. melitensis biovar 3 (QH2019001 and QH2019005) following conventional biotyping and were found to have differences in their variable number tandem repeats (VNTRs) using MLVA-16. Phylogenetic examination assigned the 96 strains to five genotype groups, with QH2019001 and QH2019005 assigned to the same group, but different subgroups. Moreover, the QH2019005 strain was assigned to a new subgenotype, IIj, within genotype II. These findings were then combined to determine the geographic origin of the two Brucella strains.Conclusions:Utilizing a whole-genome SNP-based approach enabled differences between the two B. melitensis strains to be more clearly resolved, and facilitated the elucidation of their different evolutionary histories. This approach also revealed that QH2019005 is a member of a new subgenotype (IIj) with an ancient origin in the eastern Mediterranean Sea.

简介：AbstractBackground:Arteriovenous malformation(AVM) have long-term "blood stealing" characteristics, which result in complicated hemodynamic features. To analyze the application of intraoperative indocyanine green angiography with FLOW 800 software in AVM surgeries.Methods:Data on 17 patients undergoing surgery with ICG fluorescence were collected in Beijing Tiantan Hospital. To analyze the hemodynamic features of AVM and the influence on the peripheral cortex of AVM resection, we assessed the following hemodynamic parameters: maximum intensity, slope of rise, time to half-maximal fluorescence, and transit time from arteries to veins.Results:In the 17 superficial AVMs studied, the time-delay color mode of the FLOW 800 software was superior to the traditional playback mode for identifying feeding arteries, draining veins, and their relation to normal cortical vessels. The maximum fluorescence intensity and slope of the ICG fluorescence curve of feeder arteries and draining veins were higher than those of normal peripheral vessels (P < 0.05). The transit times in AVMs were significantly shorter than those in normal peripheral vessels (P < 0.05). After AVM resection, cerebral flow increased in the cortex, and local cycle time becomes longer, although the differences were not significant (P > 0.05).Conclusions:Hemodynamic parameter analysis provided quality guidance for the resection of AVMs and could also be used in estimating changes in blood flow in the local cortex to identify abnormal hyperperfusion and residual nidus.

简介：AbstractBackground:An epidemic of COVID-19 broke out in Wuhan, China, since December 2019. The ordinary medical services were hindered. However, the emergency cases, including aneurysmal subarachnoid hemorrhage (aSAH), still required timely intervention. Thus, it provoked challenges to the routine management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China.Methods:Demographic, clinical, and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and several detailed protocols. Neurological outcomes were evaluated by the modified Rankin Scale (mRS).Results:A total of 127 aSAH were referred to our emergency department, and 42 (33.1%) underwent craniotomy clipping between January 20, 2020, and March 25, 2020. The incidence of preoperative hospitalized adverse events and the perioperative outcomes were similar (-0.1, 95% CI - 1.0 to 0.8, P = 0.779) to the retrospective period last year (January 2019-March 2019). After the propensity score matching (PSM), there were still no statistical differences in prognostic parameters between the two groups. Eight (19.0%) of the 42 individuals were initially screened as preliminary undetermined COVID-19 cases, in which 2 of them underwent craniotomy clipping in the negative pressure operating room (OR). The prognosis of patients with varied COVID-19 screening results was similar (F(2, 39) = 0.393, P = 0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission, and all showed negative. The false-negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (-0.3, 95% CI - 1.4 to 0.9, P = 0.653).Conclusions:Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.

简介：AbstractThe incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.

简介：AbstractBackground:Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.Methods:Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses.Results:Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity).Conclusion:Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.