Objective : To analyze the influencing factors associated with the coexistence of multidrug-resistantEscherichia coli(MDR-ECO) infection and active tuberculosis(ATB) in patients with lung infections. Methods: A total of 204 hospitalized patients with lung infections caused by MDR-ECO were enrolled. Among them, patients with coexisting ATB were identified and assigned to the observation group. Univariate and multivariate Logistic regression analysis were performed to identify the risk factors for the coexistence of MDR-ECO lung infection and ATB. Results : Factors such as patient age, neutrophil count, hemoglobin level, malignancy, rheumatoid arthritis, history of antibiotic exposure, and history of surgery within the past year were found to be influencing factors for the coexistence of MDR-ECO lung infection and ATB(allP<0.05). Specifically, advanced age(95%CI: 0.949-0.992,P=0.008), decreased neutrophils(95%CI: 0.750-0.922,P<0.001), and a history of antibiotic exposure(95%CI: 1.202-2.596,P=0.004) were identified as risk factors. Conclusion Some patients with MDR-ECO lung infections are prone to coexisting with ATB. Therefore, it is recommended to strengthen ATB screening among high-risk patients, including those at peak ages for susceptibility, with low neutrophil counts, and with a history of antibiotic exposure.

Objective To summarize the best evidence concerning the prevention and management of indwelling line complications in patients with hepatocellular carcinoma(HCC)receiving hepatic artery infusion chemotherapy(HAIC),and to standardize the key contents of clinical observation of complications during HAIC treatment.Methods By using the"6S"pyramid model system,the relevant literature was searched in the order from high to low.Two professionals evaluated the quality of the literature,summarized the evidence and conducted the analysis and summarization.Results Ten literature articles were finally enrolled in this study,including one article of guideline,one article of systematic review,five articles of expert consensus,one article of meta-analysis,and two articles of randomized controlled trials.Six complications(catheter displacement or falling off,catheter obstruction,unplanned extubation,arterial spasm or occlusion,infection,puncture site bleeding/local hematoma)and 22 pieces of best evidence for prevention management were summarized.Conclusion This study systematically summarizes 6 complications and their prevention and treatment in patients with HCC receiving HAIC,providing a reliable basis for clinical practice.

BACKGROUND:The effective promotion of internal angiogenesis in organoids is a current focal issue in organoid culture.Vascularized organoids,as a newly developed bioculture technology,have significant research and application value in the study of living tissue development,disease formation mechanisms,tissue replacement therapy,and drug screening.OBJECTIVE:To summarize the methods or strategies for vascularization of organoids in recent years,analyze the formation mechanism of vascularization of organoids and the construction strategies,with a view to providing reliable ideas for more in-depth study of the mechanism of organoid genesis and for clinical translation.METHODS:The authors utilized the PubMed and CNKI databases for related formation collection.The keywords were "organoids,vascularization,vascular,vascular development,vessel" in Chinese and English.Finally,77 papers were included for summarization.RESULTS AND CONCLUSION:(1) The mechanism of vascularization formation in organoid organs involves three key factors,namely seed cells,cytokines,and extracellular matrix.Seed cells provide the essential cell source for vascularized organoids;cytokines play an important role in guiding angiogenesis within organoids,and the extracellular matrix provides an external growth environment for vascular cells,promoting the occurrence of vascularized organoids.(2) The construction strategies of vascularized organoids include cell self-reorganization,microvascular fragment infiltration,transplantation into host,and microfluidic chip.In vitro induction of pluripotent stem cells to differentiate into endothelial progenitor cells can integrate with adjacent tissues and have the potential for angiogenesis,so pluripotent stem cells can be used to construct vascularized organoids by self-reorganization.Microvascular fragments retain their cellular complexity,natural structure,and phenotypic plasticity,which is more conducive to simulating natural microvessels and promoting vascularization of organoids.Transplantation into host is currently the best method to achieve complete blood perfusion in organoids,while microfluidic chip provides a solution for achieving extracorporeal blood supply in organoids.(3) Multiple construction strategies of organoid such as co-differentiation of multiple stem cell types,precise regulation of signaling molecules,microvascular infiltration,and in vivo host transplantation,have introduced vascular components into organoids to some extent,making them closer to the corresponding tissues in terms of function and maturity.However,the challenge of achieving perfusion remains,and so far,only in vivo transplantation in hosts has enabled effective perfusion in organoids.Therefore,organoids still face numerous challenges in terms of vascularization.

Objective:To investigate the impacts of nuclear receptor-interacting protein 1(NRIP1)on sepsis-evoked intesti-nal epithelial injury via transcriptional regulation of high mobility group box 1(HMGB1).Methods:The expression levels of NRIP1 and HMGB1 were detected by RT-qPCR and Western blot.The pathological changes of intestinal tissue were detected by HE staining.CCK-8 assay determined the optimal treatment time of LPS.Caco-2 cells were transfected with NRIP1 small interfering RNA(siRNA-NRIP1-1/2),and cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.RT-qPCR and Western blot examined the expressions of inflammation-associated factors.Transepithelial resistance(TEER)was used to detect intestinal epi-thelial permeability.Western blot was used to detect the expressions of apoptosis and tight-junction related proteins.The binding rela-tionship between NRIP1 and HMGB1 was verified by luciferase reporting assay and chromatin immunoprecipitation assay(ChIP).After knocking down NRIP1 and overexpressing HMGB1 in LPS-treated Caco-2 cells,the functional experiment was performed again.Results:NRIP1 expression was fortified in the intestinal tissues of sepsis rats and LPS-treated Caco-2 cells.Interference with NRIP1 attenuated LPS-elicited Caco-2 cell viability injury,apoptosis,inflammatory response and barrier damage.Additionally,NRIP1 might activate HMGB1 expression at transcriptional level and HMGB1 elevation might reverse the impacts of NRIP1 absence on Caco-2 cell viability,apoptosis,inflammatory response as well as barrier function.Conclusion:NRIP1 may promote sepsis-elicited intestinal epi-thelial injury,which may be related to transcriptional activation of HMGB1.

BACKGROUND:The effective promotion of internal angiogenesis in organoids is a current focal issue in organoid culture.Vascularized organoids,as a newly developed bioculture technology,have significant research and application value in the study of living tissue development,disease formation mechanisms,tissue replacement therapy,and drug screening.OBJECTIVE:To summarize the methods or strategies for vascularization of organoids in recent years,analyze the formation mechanism of vascularization of organoids and the construction strategies,with a view to providing reliable ideas for more in-depth study of the mechanism of organoid genesis and for clinical translation.METHODS:The authors utilized the PubMed and CNKI databases for related formation collection.The keywords were "organoids,vascularization,vascular,vascular development,vessel" in Chinese and English.Finally,77 papers were included for summarization.RESULTS AND CONCLUSION:(1) The mechanism of vascularization formation in organoid organs involves three key factors,namely seed cells,cytokines,and extracellular matrix.Seed cells provide the essential cell source for vascularized organoids;cytokines play an important role in guiding angiogenesis within organoids,and the extracellular matrix provides an external growth environment for vascular cells,promoting the occurrence of vascularized organoids.(2) The construction strategies of vascularized organoids include cell self-reorganization,microvascular fragment infiltration,transplantation into host,and microfluidic chip.In vitro induction of pluripotent stem cells to differentiate into endothelial progenitor cells can integrate with adjacent tissues and have the potential for angiogenesis,so pluripotent stem cells can be used to construct vascularized organoids by self-reorganization.Microvascular fragments retain their cellular complexity,natural structure,and phenotypic plasticity,which is more conducive to simulating natural microvessels and promoting vascularization of organoids.Transplantation into host is currently the best method to achieve complete blood perfusion in organoids,while microfluidic chip provides a solution for achieving extracorporeal blood supply in organoids.(3) Multiple construction strategies of organoid such as co-differentiation of multiple stem cell types,precise regulation of signaling molecules,microvascular infiltration,and in vivo host transplantation,have introduced vascular components into organoids to some extent,making them closer to the corresponding tissues in terms of function and maturity.However,the challenge of achieving perfusion remains,and so far,only in vivo transplantation in hosts has enabled effective perfusion in organoids.Therefore,organoids still face numerous challenges in terms of vascularization.

Objective:To investigate the impacts of nuclear receptor-interacting protein 1(NRIP1)on sepsis-evoked intesti-nal epithelial injury via transcriptional regulation of high mobility group box 1(HMGB1).Methods:The expression levels of NRIP1 and HMGB1 were detected by RT-qPCR and Western blot.The pathological changes of intestinal tissue were detected by HE staining.CCK-8 assay determined the optimal treatment time of LPS.Caco-2 cells were transfected with NRIP1 small interfering RNA(siRNA-NRIP1-1/2),and cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.RT-qPCR and Western blot examined the expressions of inflammation-associated factors.Transepithelial resistance(TEER)was used to detect intestinal epi-thelial permeability.Western blot was used to detect the expressions of apoptosis and tight-junction related proteins.The binding rela-tionship between NRIP1 and HMGB1 was verified by luciferase reporting assay and chromatin immunoprecipitation assay(ChIP).After knocking down NRIP1 and overexpressing HMGB1 in LPS-treated Caco-2 cells,the functional experiment was performed again.Results:NRIP1 expression was fortified in the intestinal tissues of sepsis rats and LPS-treated Caco-2 cells.Interference with NRIP1 attenuated LPS-elicited Caco-2 cell viability injury,apoptosis,inflammatory response and barrier damage.Additionally,NRIP1 might activate HMGB1 expression at transcriptional level and HMGB1 elevation might reverse the impacts of NRIP1 absence on Caco-2 cell viability,apoptosis,inflammatory response as well as barrier function.Conclusion:NRIP1 may promote sepsis-elicited intestinal epi-thelial injury,which may be related to transcriptional activation of HMGB1.

AIM:To observe the effect of folic acid(FA)on C2C12 myoblast proliferation and differentia-tion,and to explore its mechanism.METHODS:During the proliferation stage,C2C12 myoblasts were treated with vari-ous concentrations of FA(0,2.5,5,10 and 20 μmol/L).The cell status was observed under a microscope,cell viability was detected using the MTT method,and cell proliferation was assessed using the EdU method.In the differentiation stage,C2C12 cells were divided into control(Ctrl)group(0 μmol/L FA)and FA group(10 μmol/L FA).On day 2 or 4 of differentiation,immunofluorescence staining and Western blot were employed to detect the expression of myoblast differen-tiation-related proteins,myoblast determination protein 1(MyoD),myogenin(MyoG)and myosin heavy chain(MyHC).The myotubule formation in each group was analyzed.On day 4 of differentiation,C2C12 cells were treated with FA for 0,1,3 and 6 h,and the protein levels of p-JNK,JNK,p-p38 MAPK and p38 MAPK at each time point were detected by Western blot.Additionally,C2C12 cells after 4-day differentiation were divided into Ctrl group,FA group,FA+ SP600125(specific inhibitor of JNK)group,and FA+SB203580(specific inhibitor of p38)group.The cells in FA+ SP600125 and FA+SB203580 groups were treated with 10 μmol/L SP600125 or SB203580 for 1 h,followed by treatment with 10 μmol/L FA for 24 h.The cells in FA group were treated with 10 μmol/L FA for 24 h,while the cells in Ctrl group were left untreated.The protein levels of p-JNK,JNK,p-p38 MAPK,p38 MAPK and MyHC were detected by Western blot.RESULTS:(1)Compared with 0 μmol/L FA group,the number of the cells in other concentration groups in-creased,cell viability was raised(P＜0.05 or P＜0.01),and the rate of EdU positive cells increased(P＜0.05).(2)Com-pared with Ctrl group,the expression levels of MyoD,MyoG and MyHC in FA group were increased(P＜0.05),and the myotube fusion index was raised(P＜0.05 or P＜0.01).(3)Compared with 0 h group,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK were elevated after FA treatment for 1,3 and 6 h(P＜0.05 or P＜0.01),and showed a trend of gradual increase with the extension of treatment time.(4)After FA treatment,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK,and the expression of MyHC were elevated(P＜0.01).Treatment with SP600125 decreased the ratio of p-JNK/JNK and the expression of MyHC(P＜0.05),while SB203580 intervention cut down the ratio of p-p38 MAPK/p38 MAPK and the expression of MyHC(P＜0.05 or P＜0.01).CONCLUSION:Folic acid can promote the differentiation of C2C12 myoblasts by activating the JNK/p38 MAPK signaling pathway.

【Objective】 To explore the distribution of serological markers related to samples whose serological test results were inconsistent with HBV DNA test results among voluntary blood donors in Xi′an. 【Methods】 A total of 71 HBsAg ELISA positive and NAT non-reactive (ELISA+ /NAT-)blood samples were collected from Shaanxi Blood Center from November 1, 2022 to April 30, 2023. The serological markers of hepatitis B were detected by electrochemiluminescence method, and the HBV S region and C region gene fragments were amplified by nested-PCR. 【Results】 The positive rate of nested-PCR in double ELISA+ /NAT- group(n=30) was statistically higher than that of ELISA+ /NAT- group(n=41)(60% vs 24.4%, P<0.05). Donors in double ELISA+ /NAT- group were all first-time blood donors, with the positive rate of anti-HBc in serum of 100%, and the serological pattern was mainly positive for items 1, 4 and 5 items(80%). Among the ELISA+ /NAT- group, 31.7% were repeat blood donors, with the positive rate of anti-HBc in serum of only 19.51%, and the serological patterns were mainly single anti-HBs positive (43.90%) and all negative (36.58%). 【Conclusion】 There are false positives in the test results of ELISA+ /NAT- group, which leads to unnecessary blood discarding. Meanwhile, the samples with negative NAT may have low levels of HBV DNA, which may lead to missed detection. It is suggested that multiple systems and methods should be applied to trace the blood donors who are HBsAg positive and NAT non-reactive, so as to improve the accuracy of HBV screening of blood donors and reduce blood waste.

Objective:To explore the effects of status epilepticus(SE)on neuronal processes and synapses in the cerebral cortex and hippocampus of young mice.Methods:The young mice of SE model was established by intraperito-neal injection of lithium chloride and pilocarpine.Morris water maze test was used to detect the behavioral changes in the mice.Immunofluorescence staining was used to observe the morphological changes of axons,dendrites and synaptic connections of neurons in the cerebral cortex and hippocampus of mice,and the ultrastructural changes of synapses of pyramidal neurons in the mouse hippocampus were observed with transmission electron microscopy.Results:The sei-zure rate of grade IV and above in mice was 80％,and the mortality rate was 25％.The escape latency of SE mice was prolonged(P＜0.05),the trajectory of exploring the platform was significantly longer and more complicated,and the time spent in the target quadrant and the number of crossing the platform were significantly reduced(P＜0.05).Posi-tive expression of axonal neurofilament marker protein SMI312 and microtubule-associated protein 2(MAP2)were found in the cerebral cortex and hippocampus of both groups,and the axonal neurofilaments and neuronal dendrites in the SE group were of different lengths and arranged densely and scatteredly.The positive expression of synaptophysin(SYP)and the number of positive spots increased significantly in in the hippocampus of SE group(P＜0.01).The number of synaptic vesicles in the SE group increased significantly,and the postsynaptic density(PSD)thickness decreased significantly(P＜0.01).Conclusion:SE might lead to acute injury of synapses in the cerebral cortex and hippocampal area of young mice,induce synaptic vesicle circulation disorders,and then cause widespread destruction and disorder of the axon and dendrite networks,the reactive or compensatory reconstruction of synaptic.