Objective:To summarize the precision fluid management of patients with severe blast injury in the emergency intensive care unit, so as to help patients smoothly pass through the dangerous period and recover smoothly.Methods:Based on the experience of fluid management in 6 patients admitted to the Second Affiliated Hospital Zhejiang University School of Medicine in the tanker truck explosion on 14 June, 2020. The main measures included: fluid volume management and dynamic adjustment; assessment of intake, output and urine volume, and dynamic adjustment of infusion volume and speed; monitoring of pulmonary oxygenation and timely adjustment of fluid resuscitation strategies; monitoring indexes and providing nursing care strategies for fluid management.Results:Finally, among 6 patients with severe blast injury, 5 patients were discharged from the hospital with follow-up treatment after they suffered from the shock and infection phases and refined fluid management, 1 patient died due to severe injury and ineffective rescue.Conclusions:Adopting individualized, phased, and refined liquid management strategy has clinical significance for patients with severe blast injury to smoothly pass the risk period.

Objective:To evaluate the renal injury of ultrasound-guided percutaneous fascia dilatation with one-step and multi-step percutaneous renal dilatation on renal injury in pigs.Methods:20 experimental pigs were randomly divided into 16F group and 24F group, with 10 pigs in each group. Under the guidance of ultrasound, the left and right kidneys of each experimental pig in group 16F were expanded by percutaneous renal multi-step expansion and one-step expansion (multi-step dilation subgroup and one-step dilation subgroup respectively) with 16F expander, and the same operation was performed with 24F expander in 24F group. After the operation, the left and right kidneys were left with fistula tubes for 1 week. The duration of hematuria in the renal fistula tubes was observed and compared. One month later, the experimental pigs were killed and the kidneys were removed. The histopathology of each group was observed under the naked eye and microscope. The scar tissue around the nephrostomy channel was removed, and hematoxylin-eosin (HE) and Masson staining were performed respectively. The scar volume was measured by digital image analysis technology, and the percentage of the scar volume in the renal cortex volume was calculated.Results:There was no significant difference in gross hematuria duration between one-step dilation subgroup [(4.60±1.26)d] versus multi-step dilation subgroup [(4.70±1.17)d] of 16F group ( P>0.05); There was no significant difference in gross hematuria duration between one-step dilation subgroup [(5.40±1.25)d] versus multi-step dilation subgroup [(5.50±1.08)d] of the 24F group ( P>0.05). There was no significant difference in the gross and histological observation of pig kidney specimens in 16F group and 24F group. There was no significant difference in the scar volume of the fistula channel [(0.35±0.04)cm 3, (0.36±0.03)cm 3] and its percentage in the whole renal cortical volume [(0.41±0.05)%, (0.41±0.06)%] between one-step dilation subgroup versus multi-step dilation subgroup of 16F group (all P>0.05); there was no significant difference in the scar volume of the fistula channel [(0.48±0.02)cm 3, (0.49±0.04)cm 3] and its percentage in the whole renal cortical volume [(0.52±0.04)%, (0.53±0.07)%] between one-step dilation subgroup versus multi-step dilation subgroup of 24F group (all P>0.05). The scar volume and its percentage in the whole renal cortical volume of the one-step dilation subgroup and the multi-step dilation subgroup in the 24F group were higher than that of the 16F group, with statistically significant difference (all P<0.05). Conclusions:Both one-step and multi-step percutaneous renal dilatation have less damage to renal parenchyma. The multi-step dilatation has no obvious advantage over one-step dilatation in reducing renal parenchyma injury.

Objective : Mendelian randomization analysis was used to explore the causal relationship of T．gondii in- fection and the cyst distribution and inflammation in brain tissue by immunohistochemistry． Methods : Genome- wide association analysis data of T．gondii infection and encephalitis were obtained ，single nucleotide polymor- phisms (SNPs) were selected，Mendelian randomization analysis was conducted by inverse variance weighting，and the causal relationship between T．gondii infection and encephalitis was evaluated by OR value and 95% CI．Quality control was carried out by using heterogeneity test，horizontal multi-efficiency test and leave-one-out sensitivity test. Immunohistochemical staining was performed using brain sections of mice infected with tissue cysts of Wh6 strain for image analysis using Image J software. Results : A total of 29 SNPs were associated with toxoplasmic encephalitis. The results of IVW method suggested that T．gondii infection made encephalitis risk 0. 98 times higher ( OR = 0. 98， 95% CI = 0. 76 to 1. 27) ，indicating no causal relationship between the two．The quality control results suggested that the selected SNPs were stable and reliable．Toxoplasma cysts were distributed in various parts of the brain tis- sue． Conclusion T．gondii infection and encephalitis are related，but there is no sufficient evidence to prove the causal relationship between the two.

Objective: To investigate the distribution of toxoplasma cysts in the brain of infected mice and the effect of pathological changes on the behavior and neuropsychiatry of the mice during chronic infection with Toxoplasma gondii( T．gondii) ． Methods : Mice were infected with Prugniaud strain of T．gondii by oral gavage．The brain tissues of infected mice were collected on the days of 10，30，40，90，120 and 160 after infection respectively，and the hippocampal hypothalamus，prefrontal lobe ，striatum and cerebellum regions were separated．The number of cysts and neuropathological changes in each infected area were observed and recorded by HE staining．The number of cysts and neuropathological changes in each infected area were observed and recorded. Results : T．gondii infected mice showed symptoms of vertical hair and arched back，which were the most significant on the 40th day，and then gradually recovered with hemiplegia and circling in circles． At each time point ，the number of toxoplasma cysts was the largest in hippocampal hypothalamus，followed by prefrontal lobe and striatum，and the least in cerebellum．The diameter of toxoplasma cysts increased with time．During chronic infection，specific pathological manifestations of toxoplasma encephalitis，such as neuronophagy，were observed in all regions of the brain tissue．The above pathological changes of toxoplasma encephalitis reached the peak on the 40th day，and gradually recovered， and increased to the stimulation peak on the 120th day，and then gradually recovered． Conclusion The behavioral and neuropsychiatric symptoms of T．gondii during chronic infection were correlated with the localization and distribution of toxoplasma cysts in the brain of infected mice，and showed dynamic changes.

BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.