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.

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 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.

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 investigate the effects of cigarette smoke exposure during adolescence on the inflammato-ry response mediated by microglia in the prefrontal cortex of mice,and its impact on learning and memory functions in adulthood.METHODS:72 two-week-old healthy male Kunming mice,with each weighing(11.0±1.5)g,were random-ly divided into control and cigarette exposure groups(n=36 per group).The mice in the cigarette exposure group were pas-sively exposed to 6 cigarettes daily for 10 weeks.At three time points of 4-week-old(infancy),8-week-old(adoles-cence),and 12-week-old(adulthood),six mice were selected from each group to have their neurobehavioral and patholog-ical changes examined.In particular,the step-down test,three-chamber social interaction test,and novel object recogni-tion test were used to detect changes in learning and memory abilities and cognitive behavior.Immunofluorescence testing was performed to detect the morphology,number of synapses,and expression of inflammatory factor apoptosis-associated speck-like protein containing a CARD(ASC)around the microglial cells in the prefrontal cortex of mice in each group.Western blot was performed to assess the expression levels of synaptophysin(SYP)and postsynaptic density protein-95(PSD-95)in the cerebral cortex of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the protein expression of tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),and IL-6 in the prefrontal cor-tex.RESULTS:(1)In the step-down test,the latency of mice at 8 and 12 weeks of age was significantly shortened,and the number of errors was significantly increased in the cigarette exposure group compared with the age-matched control group(P＜0.01).In addition,the social recognition time and exploration time for novel objects were prolonged(P＜0.05).(2)Immunofluorescence assays revealed that exposure to cigarette smoke in mice,at both 8 and 12 weeks of age,resulted in a reduction of SYP-positive puncta within the prefrontal cortex.Concurrently,there was an observed increase in the number of Iba1-positive microglia,which exhibited an activated phenotype,as well as an elevation in ASC-positive puncta in proximity to the microglia.Western blot further revealed reduced expression of synaptophysin protein SYP and PSD-95 in the cerebral cortex of the mice at 8 and 12 weeks of age in the cigarette exposure group(P＜0.05).(3)ELISA showed increased levels of inflammatory factors TNF-α,IL-1β,and IL-6 in the prefrontal cortex of the mice at 8 and 12 weeks of age in the cigarette exposure group(P＜0.05).CONCLUSION:Exposure to cigarette smoke during adoles-cence in mice may result in the enhanced secretion of inflammatory factors through the activation of microglia in the pre-frontal cortex.This activation can alter microglial function and induce synaptic damage,consequently impairing learning,memory,and cognitive abilities in adulthood.

Objective To investigate the clinical and practical value of transvaginal endoscopic technology by using traditional hysteroscope in the diagnosis and treatment of intrauterine lesions in asexual women of childbearing age.Methods A retrospective analysis was conducted on 98 cases of hysteroscopic surgery in asexual women of childbearing age admitted from January 2005 to May 2024.Transvaginal endoscopic technology was applied for hysteroscopic examination and/or treatment by using traditional hysteroscope.Results A total of 62 cases underwent electrocautery after cervical dilation with a dilation rod,including 43 cases of endometrial polyps,15 cases of submucosal fibroids,and 4 cases of cervical polyps.The remaining 36 cases underwent endometrial biopsy or curettage by using a microscope,and all obtained endometrial biopsy pathology.One case of hymen laceration about 0.3 cm in length was sutured with 5-0 absorbable suture for one stitch.For the remaining cases,the hymen remained intact.Conclusion Using transvaginal endoscopic technology with traditional hysteroscope can complete hysteroscopic examination or surgical treatment without damaging the hymen,which is suitable for asexual women of childbearing age.

Objective:To evaluate the mood and psychological state of pregnant women with different working states and analyze the influence of working on depression state during the entire pregnancy.Methods:A total of 396 women aged 20-45 years were prospectively enrolled in Capital Medical University Affiliated Beijing Tian Tan Hospital in early pregnancy from December 2020 to April 2020. The ones who had a history of depressive disorder, bipolar disorder, and other mental disorders were excluded. Their psychological states were assessed by the Edinburgh Postnatal Depression Scale (EPDS), the Fatigue Severity Scale (FSS), and the Connor-Davidson Resilience Scale (CD-RISC) at baseline, the second and third trimester of pregnancy accordingly. Based on employment status during pregnancy, they were analyzed into Full-time (252 cases), Part-time (97 cases), and Unemployed (47 cases) groups. A 3 (Group) ×3 (Pregnancy trimester) repeated measures ANOVA was used to compare the differences in EPDS scores among the three groups. Multivariate Linear Regression was used to analyze the effects of employment status and other factors on EPDS scores during pregnancy.Results:Compared to the Full-time and Part-time employment groups, the Unemployed group had lower education levels and higher FSS scores [ones who own a bachelor′s degree or below: 85.2% (40/47) vs 64.3% (162/252); FSS score: (37.5±9.3) vs (33.1±11.2)] (all P<0.05). Repeated measures ANOVA showed the main effect of group and time on EPDS depression scores was statistically significant ( F=3.19, P=0.043; F=6.20, P=0.002). EPDS scores in early pregnancy were significantly higher than those in late pregnancy [(0.6±0.01) vs (0.5±0.01), P=0.003]. There was no significant difference in EPDS scores among different groups ( PBonferroni correction >0.017). There were no statistically significant interaction effects between the three groups and three trimesters of pregnancy ( F=1.34, P=0.253). Regression analysis results showed that Full-time or Part-time employment, higher marital satisfaction, better psychological resilience contributed fewer depression scores in the second trimester of pregnancy ( R 2adjusted=0.34, F=22.37, P<0.001). Conclusion:Both Full-time and Part-time employment during pregnancy have a positive impact on depressive mood in the second trimester of pregnancy but probably no impact in the early and late pregnancy.