Objective To evaluate the effect of LifePort combined with polymyxin B in preventing donor-derived infections caused by preservation solution contamination. Methods Clinical data of 110 kidney transplant recipients were retrospectively analyzed. According to the decontamination status of preservation solution, the recipients were divided into the decontamination group (n=62) and the non-decontamination group (n=48). The general data of the two groups were compared, and the preventive effect of polymyxin B on possible donor-derived infections (p-DDI) was analyzed, especially infections associated with multidrug-resistant Gram-negative bacteria (MDR GNB). Results There were no statistically significant differences in baseline data (gender, age, preservation solution contamination status, etc.) between the decontamination group and the non-decontamination group (all P > 0.05). The overall contamination rate of preservation solution was 80.0%, and 68 contaminated samples were with single microorganism and 20 with multiple microorganisms. Coagulase-negative staphylococci, Enterococcus and Klebsiella pneumoniae were the most common microorganisms in the positive samples. Fifteen cases of preservation solution were contaminated by MDR GNB, including 10 cases in the non-decontamination group and 5 cases in the decontamination group, with no statistically significant difference between the two groups (P = 0.053). Postoperative infection-related events occurred in 69 recipients, including 39 cases in the non-decontamination group and 30 cases in the decontamination group, with the incidence rate in the non-decontamination group significantly higher than that in the decontamination group (P < 0.001). Only 10 cases of infections were identified as p-DDI, all of which were positive for preservation solution culture, including 8 cases in the non-decontamination group and 2 cases in the decontamination group (P < 0.05). There were 5 cases of p-DDI related to MDR GNB in the non-decontamination group, while no such cases occurred in the decontamination group (P < 0.05). No adverse reactions related to polymyxin B were observed, and no recipient death or renal allograft dysfunction occurred in either group. Conclusions Adding polymyxin B to the preservation fluid during hypothermic machine perfusion with LifePort before renal transplantation may reduce p-DDI and its potential adverse consequences.

Objective : To explore the effect and mechanism of total saponins of astragalus membranaceus combined with bone marrow mesenchymal stem cells (BMSCs) regulating the stromal cell-derived factor-1 (SDF-1) / chemo- kine receptor 4 ( CXCR4) pathway in the treatment of autoimmune premature ovarian failure ( POF) model rats． Methods : Rats were randomly divided into POF group，total saponins of astragalus membranaceus group，BMSCs group ，combination group ，combination + SDF-1 / CXCR4 pathway inhibitor ( AMD3100 ) group ，and control group，with 12 rats in each group．Except for the control group，all other groups of rats needed to construct a POF model．After successful modeling，treatment would begin．The drug injected into the tail vein once a week，and the drug injected into the abdominal cavity once a day for 4 weeks．ELISA was applied to detect the levels of anti ovari- an antibodies (AOAB) ，β-endorphin ( β-EP) ，vascular endothelial growth factor (VEGF) ，tumor necrosis factor- α (TNF-α) ，and interferon-γ ( INF-γ) in serum．Changes in ovarian index were detected．HE staining was ap- plied to detect the number of mature follicles，developing follicles，and blocked follicles in the ovary．Flow cytome- try was applied to detect the proportion of BMSCs in the ovaries．QRT-PCR was applied to detect the mRNA ex- pression of mesenchymal transition factor (cMET) ，hepatocyte growth factor (HGF) ，SDF-1，and CXCR4 in ovar- ian tissue．Western blot was applied to detect SDF-1 and CXCR4 proteins in ovarian tissue． Results : Compared with the control group，the serum levels of AOAB，TNF-α , INF-γ , and the number of blocked follicles in the ova- ries were higher，while the serum levels of β-EP，VEGF，ovarian index，the numbers of mature follicles and devel- oping follicles in the ovary，the expression of SDF-1，CXCR4 mRNA and protein were lower in the POF group (P < 0. 05) ．Compared with the POF group，the serum levels of AOAB，TNF-α , INF-γ , and the number of blocked follicles in the ovaries were lower，while the serum levels of β-EP，VEGF，ovarian index，the numbers of mature follicles and developing follicles in the ovary，the proportion of BMSCs，the expression of cMET ，HGF，SDF-1， CXCR4 mRNA and SDF-1，CXCR4 protein were higher in the total saponins of astragalus membranaceus group， BMSCs group，and combination group，and the corresponding indicators in the combination group showed the most obvious change trend (P＜0. 05) ．AMD3100 reversed the effect of total saponins of astragalus membranaceus com- bined with BMSCs on POF rats． Conclusion The combination of total saponins of astragalus membranaceus and BMSCs may inhibit inflammation in POF rats，promote follicular development，increase the proportion of BMSCs in the ovaries，and promote their homing by activating the SDF-1 / CXCR4 pathway，thereby improving ovarian func- tion．

Objective To establish a prediction model for in-hospital mortality risk in patients with sepsis-induced coagulopathy based on LASSO regression.Methods Patients with sepsis-induced coagulopathy ad-mitted to intensive care unit(ICU)at Beth Israel Deaconess Medical Center during 2008 to 2019 were selected from the Medical Information Market for Intensive Care(MIMIC)-Ⅳ database(version 2.1)for retrospective study.The study subjects were randomly divided into modeling group and verification group,and the feature variables were screened by LASSO regression.The feature variables were analyzed by multivariate Logistic re-gression to determine independent risk factors,and the nomogram prediction model was established at the same time.The model performance was evaluated by drawing calibration curve and receiver operating charac-teristic(ROC)curve,as well as decision curve analysis.Results A total of 4 994 patients with sepsis-induced coagulopathy admitted to ICU for the first time were enrolled in this study.They were randomly divided into a model group(n=3 495)and a validation group(n=1 499)at a ratio of 7:3.Multivariate Logistic regres-sion analysis showed that age,mean respiratory rate,mean corpuscular hemoglobin concentration,red blood cell count,platelet count,prothrombin time,anion gap,acute physiological score Ⅲ and acute kidney injury were independent risk factors for in-hospital mortality of patients with sepsis-induced coagulopathy.Based on the above independent risk factors,a nomographic prediction model was constructed.The area under the ROC curve and 95％confidence interval of the nomogram in the modeling group and validation group were 0.864(0.849-0.880)and 0.877(0.852-0.901),respectively.The sensitivity was 0.795 and 0.763,and the speci-ficity was 0.779 and 0.843,respectively.The calibration curve suggested that the predicted probability was ba-sically consistent with the actual probability,and the decision curve analysis showed that it had good clinical net benefits within a wide range of threshold.Conclusion The nomogram model based on MIMIC-Ⅳ database has good predictive value for predicting the in-hospital mortality of patients with sepsis-induced coagulopathy and can be used to guide clinical work.

Objective:To investigate the effects and mechanisms of Nicorandil, an ATP-sensitive potassium channel (KATP) opener, on pyroptosis and inflammatory responses in microglia(BV2) induced by oxygen-glucose deprivation/reoxygenation (OGD/R).Methods:BV2 cells were divided into control group, OGD/R group, and OGD/R+ Nicorandil group.And the cells were subjected to oxygen-glucose deprivation for 3 hours and then reoxygenated for 24 hours to establish an OGD/R cell model. OGD/R+ Nicorandil group cells were incubated with 5 μg/mL Nicorandil culture medium for 24 hours after oxygen-glucose deprivation for 3 hours.The cell proliferation activity was detected by CCK8 assay.Calcein/propidium iodide (calcein/PI) assay kit was used to detect the membrane porosity rupture rate of cell in each group.Western blot analysis was performed to detect the protein expression levels of nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), inhibitor of nuclear factor-κB α(IκB-α), phosphorylated IκB-α (p-IκB-α), absent in melanoma 2 (AIM2), cleaved-caspase-1, gasdermin D-N (GSDMD-N), interleukin-18 (IL-18), and interleukin-1β (IL-1β). Immunofluorescence was used to detect the protein expression levels of AIM2 and GSDMD-N in each group. Statistical analysis was performed by SPSS 26.0 software. One-way ANOVA was used for multiple group comparisons, and LSD test was used for pairwise comparisons.Results:(1) There were statistically significant differences in the membrane porosity rupture rates among the three groups ( F=615.882, P<0.05). The membrane porosity rupture rate in the Nicorandil group was lower than that in the OGD/R group ((41.50±3.04)%, (59.44±3.66)%, P<0.05). (2) Western blot results showed that the protein expression levels of p-NF-κB, NF-κB, p-IκB-α, and IκB-α were significantly different among the three groups ( F=10.000, 62.652, 67.121, 101.023, all P<0.05). The levels of p-NF-κB, NF-κB and p-IκB-α in the OGD/R+ Nicorandil group ((0.60±0.13), (0.87±0.06), (0.55±0.06), respectively) were lower than those in the OGD/R group ((1.02±0.09), (1.03±0.09), (0.86±0.04), respectively) (all P<0.05). The level of IκB-α in the OGD/R+ Nicorandil group ((0.63±0.05), (0.46±0.06)) was higher than that in the OGD/R group( P<0.05). (3) The protein expression levels of AIM2, cleaved-caspase-1, GSDMD-N, IL-18, and IL-1β were significantly different among the three groups ( F=65.926, 12.428, 66.447, 44.831, 52.960, all P<0.05). The levels of AIM2, cleaved-caspase-1, GSDMD-N, IL-18 and IL-1β in the OGD/R+ Nicorandil group ((0.78±0.04), (0.71±0.09), (0.54±0.04), (0.72±0.07), (0.50±0.08), respectively) were lower than those in the OGD/R group ((0.94±0.09), (0.89±0.09), (0.85±0.04), (0.90±0.07), (0.99±0.03), respectively) (all P<0.05). (4) Immunofluorescence results showed statistically significant differences in the fluorescence intensity of pyroptosis marker proteins AIM2 and GSDMD-N among the three groups ( F=36.353, 46.817, both P<0.05). The fluorescence intensities of AIM2 ((124.36±7.91), (140.19±5.63)) and GSDMD-N ((134.16±5.18), (147.45±5.63))in the OGD/R+ Nicorandil group were lower than those in the OGD/R group (both P<0.05). Conclusion:Nicorandil can mitigate BV2 cell damage following oxygen-glucose deprivation, inhibiting the release of pro-inflammatory factors. The mechanism may be related to the downregulation of the expression of NF-κB related proteins and inhibition of AIM2 inflammasome-mediated pyroptosis after OGD/R.

Acute kidney injury (AKI) is caused by a variety of diseases, which leads to acute renal function decline, azotemia, water and electrolyte disorders and acid-base balance disorders. Metabolomics is a research method that can quantitatively analyze all metabolites in an organism and find the relative relationship between metabolites and physiological and pathological changes. In recent years, several metabolites screened based on metabolomics have been proposed as potential biomarkers to assess the early development and prognosis of AKI and for the discovery of unknown potential therapeutic targets. Based on metabolomics, this paper reviews the risk prediction, early diagnosis, disease monitoring, prognosis assessment and the application of corresponding drugs for AKI, so as to provide reference for precision medicine.
Humans ; Acute Kidney Injury/metabolism* ; Metabolomics ; Prognosis ; Biomarkers ; Precision Medicine

Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis, and highlight questions that might have a potential impact in the future.

Objective Explore the diagnosis experience of sarcomatoid renal cell carcinoma (SRCC).Method There were 5 cases of SRCC from April 2011 to June 2013,3 of them were females and 2 were males,with a mean age of 49 (27-71).All the patients were presented with pain accompanied with other symptoms such as hematuria,fever and polyuria.CT urography suggested renal occupied lesions,withuneven density and enhancement,and malignancy was highly suspected.The mean diameter of tumors was 9.2 cm(4-18 cm).Radical nephrectomy was performed on all patients,tumors were located in renal parenchymal,and with adherence to other tissues.One patient with lung metastasis was found before surgery.Result Pathologic findings of the resected tissues after operation noted SRCC.Under the microscope,a large number of spindle shaped cells were seen,and Vimentin and PCK were all positive in immunohistochemical.Three patients with metastases were found after surgery (adrenal gland,liver,pancreas).Postoperative pathological stages were one T2N0M1,three T4N0M1 and one T3N0M0.One patient received IL-2 immunotherapy.All patients died within 9 months after surgery with a median survival of 3.8 months.Immunohistochemistry in the postoperative,there were four patients with the level of Ki-67 LI ＞ 50％,with distant metastasis and survival time was 1-4 moths.Conclusion The disease develops rapidly,and the prognosis of the patients is very poor.The Ki-67 LI may be considered as a prognosis marker and the patients with sarcomatoid differentiation can benefit little from surgery alone.

Objecflve To study the heredity and variance of E1 gene of rubella villls Matsuba vac-cine strain.and to evaluate the protective efficacy of the vaccine prepared by Matsuba vaccine strain on genelevel.Methods The Matsuba strain was passaged on primary rabbit kidnev cells from 14 to 23 generations.and the E1 genes of 14,16,17,18,23 passages amplified by RT-PCR were cloned into the T-A cloning vector pGEM-T and sequenced,respectively.The sequences of E1 gene of the passaged viruses were tom-pared with rubella virus Matsuba reference strain E1 gene(Accession No.D50673)and other rubella strains in GenBank.respectively.Results The Matanba passaged shared higher homology of nucleotide and amino acid with Matsuba reference strain(D50673).,The sequences of nucleotide and amino acid of RV14,RV16.RV18 were identical to D50673.The homology of nucleotide sequences of RV17,RV23 and D50673 was 99.9%and 99.7%,respectively,andthe homology of amino acidwgg 99.8% and 99.2%,respective-ly.The amino acid related to glycosylation and epitopes of the passage viruses were highly conservative.The phylogenetic tree showed Matsuba strain belonged to la genotype.The rubella virus genotypes circulated in China recent years were 1E,lF,2A and 2B,and 1E genotype was the predominant genotype.The homology of nucleotide and amino acid of Matsuba strain and the other genotype reference strains was 92.1%-99.6% and 98.1%-99.8%.respectively.Condusion The Matsuba vaccine strain possesses highly genetic stabil-ity.which indicates that the Matsuba strain and its vaccine are stable on molecular level.And the vaccine prepared by Matsuba vaccine strain can prevent the infection of various genotype rubella viruses.