Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Objective : To establish a method for measuring major organic acids in the tricarboxylic acid cycle using a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) system, and to investigate the changes in six tricarboxylic acid cycle organic acids(fumaric acid, malic acid, succinic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid) in the serum, liver, and placenta of mice exposed to di(2-ethylhexyl) phthalate(DEHP) during pregnancy. Methods : The serum, liver and placental samples from pregnant mice were processed and eluted through a Waters ACQUITY UPLC BEH Amide Column(130 Å, 1.7 μm, 2.1 mm × 150 mm) using a gradient elution program. Mobile phase A comprised an aqueous solution of 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, while mobile phase B consisted of a 90% acetonitrile aqueous solution containing 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, with a flow rate maintained at 0.35 ml/min. The mass spectrometry detection system utilized an electrospray ionization technique with negative ion mode for multiple reaction monitoring. Results : The correlation coefficients of the standard curves for the six tricarboxylic acid cycle organic acid metabolites were all above 0.996 within the quantitative range. The method's accuracy ranged from 97.14% to 108.26%, with inter-day and intra-day precision relative standard deviation between 1.35% and 6.73%. The matrix effect was between 93.29% and 107.47%, and the extraction recovery rate ranged from 94.82% to 112.57%. Analysis of six tricarboxylic acid cycle organic acids in the liver, serum, and placenta of DEHP-exposed mice during pregnancy showed significant reductions in fumaric acid, malic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid compared to the control group(P<0.05). Conclusion The HPLC-MS/MS method established in this study for detecting six tricarboxylic acid cycle organic acids in the serum, liver, and placenta of DEHP-exposed pregnant mice is stable, highly sensitive and selective. Prenatal DEHP exposure induced alterations in the levels of tricarboxylic acid(TCA) cycle organic acid metabolites in the liver, serum, and placenta of mice, suggesting that DEHP exposure during pregnancy may interfere with mitochondrial TCA cycle processes. These findings indicate potential value in the diagnosis and treatment of diseases associated with prenatal DEHP exposure.

Objective:To construct a double-closed-loop management model for medical equipment and explore its application value in hemodialysis machine maintenance and fault management.Methods:Based on the closed-loop management of clinical operation of medical equipment and the closed-loop management of technical support,a dual closed-loop management model of equipment was constructed.65 hemodialysis machines in clinical use in Huashan Hospital Fudan University from January 2021 to January 2023 were selected and divided into a conventional mode and double-closed-loop mode according to different management modes.The conventional mode adopted conventional equipment management methods,and the double-closed-loop mode adopted a double-closed-loop management model.The cost-effectiveness,social benefit,failure occurrence,effective management quality matters,disinfection status,average patient waiting time and satisfaction were compared between the two groups.Results:The hemodialysis machine operating profit growth rate,diagnosis and treatment cost growth rate,service life index,scientific research service growth rate,diagnosis and treatment service growth rate,startup rate and operation rate of the double-closed-loop mode were(3.95±1.04)%,(3.80±0.58)%,(1.58±0.31)%,(4.30±0.95)%,(7.91±1.58)%,(96.58±2.76)%and(89.90±5.58)%,which were higher than those of the Conventional mode,the difference was statistically significant(t=5.418,10.070,7.490,17.570,11.820,8.849,6.840,P<0.05).The technical support expenses growth rate,bacterial colony count,bacterial endotoxin content and average patient waiting time of patients in the Double-closed-loop mode were(2.60±0.33)%,(0.370±0.008)cfu/ml,(0.0063±0.0011)EU/ml and(0.76±0.13)h,which were less than those of the conventional mode,the difference was statistically significant(t=23.040,82.985,14.482,19.530,P<0.05).The incidence rate of hemodialysis machine failure in the double-closed-loop mode was 9.23%(6/65),which was lower than that in the conventional mode,the difference was statistically significant(x2=6.392,P<0.05);among the 120 items of management data collected,quality control testing,maintenance and repair,clinical operation,information data,and scrap processing effectiveness rates were 95.83%(115/120),89.17%(107/120),96.67%(116/120),95.00%(114/120),and 97.50%(117/120),respectively,which were higher than those of the conventional mode,the difference was statistically significant(x2=15.238,16.596,9.808,15.585,16.119,P<0.05).Conclusion:The application of closed-loop management model to hemodialysis machine maintenance and fault management can effectively improve equipment cost-effectiveness,social benefits,management quality and patient satisfaction,and reduce the incidence of faults.

Objective To investigate the distribution and antimicrobial resistance of the bacterial strains isolated from blood samples of inpatients in Longgang Hospital,Beijing University of Chinese Medicine.Methods The bacterial identification and antimicrobial susceptibility test results for the strains isolated from 2018 to 2022 were retrospectively analyzed.Results A total of 910 strains of bacteria were isolated from blood samples,of which 63.2％(575/910)were gram-negative bacteria and 36.8％(335/910)were gram-positive bacteria.Escherichia coli,coagulase-negative Staphylococcus,Klebsiella pneumoniae,Staphylococcus aureus,and Enterococcus spp.were the top 5 pathogens.In the past 5 years,no carbapenem-resistant strains of E.coli or K.pneumoniae were found in the blood samples of the inpatients.A.baumannii had a resistance rate of 11.8％to carbapenems.The prevalence of methicillin-resistant strains in S.aureus,S.epidermidis and other Staphylococcus species was 16.7％,75.0％and 55.5％,respectively.No vancomycin-or linezolid-resistant staphylococcual isolates were found.No strains of Enterococcus faecalis or Enterococcus faecium were found resistant to high concentrations of gentamicin,linezolid,or vancomycin.Conclusions The bacteria isolated from blood samples in Longgang Hospital were mainly gram-negative bacteria.Carbapenem-resistant strain was identified in the strains of A.baumannii.Bacterial resistance surveillance should be strengthened for the isolates from blood samples and other specimens from the site of infection.Antimicrobial agents should be used rationally to prevent the spread of drug-resistant bacteria.

Objective To investigate the effects and mechanisms of five-element music on the social behavior of the children of mothers with fear stress during pregnancy and provide a basis for the early prevention and treatment of clinical fetogenic affective disorders.Methods Forty-five pregnant mice were randomly divided into three groups:a control group,model group,and five-element music group.The model and five-element music group models were established using the bystander electric shock method.Additionally,the five-element music group was exposed to Palace Tune five-element music daily from 17:00 to 19:00 during pregnancy.On the 19th day of pregnancy,ELISA was employed to assess the levels of adrenocorticotropin(ACTH)and cortisol(CORT)in the serum of pregnant mice in each group for modeling evaluation.The offspring were subsequently grouped with their mother and underwent an 8-week-old three-box social experiment to observe their social behavior.We used the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the medial prefrontal cortex(mPFC)of the offspring.High-performance liquid chromatography was employed to measure the total glutamate(Glu)content in the mPFC,while Gorky staining was used to observe changes in the dendritic spines of mPFC neurons in the offspring.Results Compared to those in the blank group,pregnant mice in the model group exhibited a significant increase in the levels of ACTH and CORT in their serum,and there was a significant decrease in the social interaction time and social novelty preference index of their offspring.There was also a significant decrease in glutamate neuron activity,glutamate content,and neuronal dendritic spine density.In contrast,compared with those in the model group,pregnant mice in the five-element music group demonstrated a reduction in the levels of ACTH and CORT in the serum,and there were improvements in the social behavior,glutamate neuron activity,glutamate content,and condition of neuronal dendritic spines in the offspring.Conclusions Intervention with five-element music effectively ameliorated the offspring's social behavior disorder result ing from prenatal fear stress;the mechanism was potentially linked to enhanced glutamate neuron activity in the mPFC region.

Objective To explore the promoting effect of egg yolk oil combined with heat-clearing and detoxi-fying traditional Chinese medicine external washing on postoperative wound healing in patients with perianal abscesses based on growth factors in the wound granu-lation tissue.Methods Eighty patients with perianal abscesses admitted to our hospital from January 2023 to May 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.Three days after surgery,the control group received routine treatment,such as external washing with heat-clearing and detoxifying Chinese herbal medicine and dressing changes with vase-line gauze.The observation group received additional treatment with egg yolk oil,and both groups were treated continuously for 7 days.The clinical efficacy,improvement in clinical symptoms,and wound recovery at different time points;serum inflammatory cytokines;and expression levels of wound granulation tissue-related factors were compared between the two groups.Results The total effective rate was higher in the observation group than the control group(95%vs.75%,P<0.05).The time of pruritus disappearance,decaying flesh,emer-gence of new epithelium,and healing were shorter in the observation group than in the control group(P<0.05).The pain degree,wound secretion,granulation morphology and surrounding tissue edema score of the observation group were significantly decreased at 7 and 10 days after surgery compared with the control group(P<0.05).Serum levels of interleukin(IL)-1β,IL-8,and tumor necrosis factor-α were lower in the observation group than the control group at 7 and 10 days after surgery(P<0.05).The levels of basic fibroblast growth factor,vascular endothelial cell growth factor,and transforming growth factor-βin wound granulation tissue were higher in the observation group than the control group at 7 and 10 days after surgery(P<0.05).Conclusion The external application of egg yolk oil combined with heat-clearing and detoxifying Chinese herbs can significantly improve the clinical symptoms of patients with perianal abscesses and promote wound healing,with significant therapeutic effects.This may be related to the inhibition of inflammatory cytokine expression and the promotion of wound granulation tissue growth factor expression.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common complication after liver transplantation, which could prolong the length of postoperative intensive care unit stay, affect clinical efficacy of liver transplantation and even lead to the death of recipients. ALI/ARDS has attracted extensive attention from liver transplant surgeons in clinical practice. ALI/ARDS after liver transplantation may be directly caused by pulmonary factors (such as mechanical ventilation-related lung injury, lung infection and aspiration, etc.) or indirectly induced by non-pulmonary factors (such as severe infection outside the lungs, blood transfusion and ischemia-reperfusion injury, etc.). In this article, the diagnostic criteria, incidence, mechanism, risk factors, laboratory and clinical diagnostic approaches and treatment of ALI/ARDS after liver transplantation were reviewed, aiming to deepen the understanding and cognition of ALI/ARDS during the perioperative period of liver transplantation and provide reference for the diagnosis and treatment of ALI/ARDS following liver transplantation.

Studies on diabetes have long been hampered by a lack of authentic disease models that, ideally, should be unlimited and able to recapitulate the abnormalities involved in the development, structure, and function of human pancreatic islets under pathological conditions. Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets. Thus, islet organoids hold great promise for modeling islet development and function, deciphering the mechanisms underlying the onset of diabetes, providing an in vitro human organ model for infection of viruses such as SARS-CoV-2, and contributing to drug screening and autologous islet transplantation. However, the currently established islet organoids are generally immature compared with native islets, and further efforts should be made to improve the heterogeneity and functionality of islet organoids, making it an authentic and informative disease model for diabetes. Here, we review the advances and challenges in the generation of islet organoids, focusing on human pluripotent stem cell-derived islet organoids, and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.
COVID-19 ; Diabetes Mellitus/therapy* ; Humans ; Islets of Langerhans ; Organoids ; SARS-CoV-2

Background::Sepsis is a systemic inflammatory syndrome induced by several infectious agents. Multiple organs are affected by sepsis, including the liver, which plays an important role in metabolism and immune homeostasis. Fibroblast growth factors (FGFs) participate in several biological processes, although the role of FGF5 in sepsis is unclear. Methods::In this study, lipopolysaccharide (LPS) was administrated to mice to establish a sepsis-induced liver injury. A similar in vitro study was conducted using L-02 hepatocytes. Western blot and immunohistochemistry staining were performed to evaluate the FGF5 expression level in liver tissues and cells. Inflammatory cell infiltrations, cleaved-caspase-3 expressions, reactive oxygen species and levels of inflammatory cytokines were detected by immunofluorescence, dihydroethidium staining, and reverse transcription quantitative polymerase chain reaction analysis, respectively. Flow cytometry was used to detect the apoptosis level of cells. In addition, ribonucleic acid (RNA)-sequencing was applied to explore the possible mechanism by which FGF5 exerted effects. Results::LPS administration caused FGF5 down-regulation in the mouse liver as well as in L-02 hepatocytes. Additionally, with FGF5 overexpression, liver injury and the level of hepatocyte apoptosis were ameliorated. Further, RNA sequencing performed in hepatocytes revealed the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway as a possible pathway regulated by FGF5. This was supported using an inhibitor of the PI3K/AKT pathway, which abrogated the protective effect of FGF5 in LPS-induced hepatocyte injury. Conclusion::The anti-apoptotic effect of FGF5 on hepatocytes suffering from LPS has been demonstrated and was dependent on the activation of the PI3K/AKT signaling pathway.

Objective:Bioinformatics method was used to screen out prognostic model constructed by the tumor microenvironment (TME)- related genes of adrenocortical carcinoma (ACC), and the prognostic model was verified to provide clinical guidances and related biomarkers for the diagnosis and treatment of ACC.Methods:Transcriptome and clinicopathological data of 79 ACC patients were collected from the Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was used to calculate immune score, stromal score (both reflect TME) and ESTIMATE score; VennDiagram was used to select differentially expressed genes among immune score, high and low stromal score groups (grouped by median value); Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genome (KEGG) database were used to perform functional enrichment analysis on selected genes and to explore the potential function and pathway of genes. Univariate Cox analysis, lasso regression analysis and multivariate Cox analysis were used to screen out genes related to ACC TME and to establish risk score (RS) model for ACC patients. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of RS. The data sets GSE33371 and GSE19750 of Gene Expression Omnibus (GEO) were used as external validation sets to validate the prognostic model. The data of 79 ACC patients were extracted from the TCGA database, and the clinicopathological factors and the RS of the established prognostic model were included in the Cox regression analysis to obtain the prognostic factors of ACC patients.Results:According to the immune score and stromal score, 1 205 differentially expressed genes from intersection of both scores were screened out by using VennDiagram, including 833 up-regulated genes and 372 down-regulated genes. After continuing the regression analysis and screening of differentially expressed genes, the ACC prognostic model containing 9 TME-related genes (GREB1, POU4F1, HIC1, HOXC9, CACNB2, RAB27B, ZIC2, C3, CYP2D6) was finally constructed, that was, RS = GREB1×0.223 6+POU4F1×0.671 7+HIC1×0.167 5+HOXC9×0.211 3+CACNB2×0.156 0+RAB27B×0.956 5+ZIC2×0.582 7+C3×(-0.003 1)+CYP2D6×0.819 3. The area under the curve (AUC) of ROC for the 1, 3, and 5-year overall survival of 79 ACC patients predicted by the model in the TCGA database was 0.876, 0.919, 0.917, respectively. In the GEO validation set, the AUC of the 1, 3, and 5-year overall survival for 45 ACC patients predicted by the model was 0.689, 0.704, and 0.708, respectively, indicating that the model had a high prediction accuracy for survival results of ACC patients. Cox regression analysis on the data of 79 ACC patients in the TCGA database showed that the TME-related gene prognostic model RS was an independent factor influencing the prognosis of ACC patients ( HR = 1.011, 95% CI 1.005-1.016, P < 0.01). Conclusions:The established ACC TME-related gene prognostic model can be used to predict the prognosis of ACC patients. The model including 9 genes may become a new target for studying the pathogenesis and immunotherapy of ACC, and it is worthy of further research.