Sepsis is a lethal condition resulting from the host's dysregulated response, involving complex pathophysiological mechanisms, including the host's biphasic immune response and metabolic disturbances. Diagnosing and treating sepsis remain formidable challenges, with the absence of definitive biomarkers and effective therapeutic interventions to date. Animal models of sepsis are pivotal in unraveling the disease's pathogenesis and identifying potential treatments, playing a crucial role in enhancing our comprehension of its intrinsic nature. However, there is no animal model that can comprehensively and accurately simulate the complex pathophysiological process of human sepsis. This review discusses the widely used sepsis animal models, exploring their advantages and limitations in terms of pathogenesis, inflammatory response, pathophysiological changes, and organ dysfunction. It summarizes the application scenarios and latest research advancements of these models and provides an outlook on potential future improvements.
Sepsis/physiopathology* ; Animals ; Disease Models, Animal ; Humans

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective To explore the risk factors for the recurrence of autoimmune pancreatitis(AIP),so as to provide a new reference for its clinical treatment.Methods The clinical data of 198 AIP patients admitted to The First Affiliated Hospital of Naval Medical University from 2014 to 2021 were collected,including 164 patients with type 1 AIP and 34 patients with type 2 AIP.Based on the recurrence status of AIP,the patients were categorized into recurrence group(38 cases)and non-recurrence group(160 cases),and differences between the 2 groups were analyzed.Patients with definite duration of glucocorticoid maintenance therapy were further screened,and logistic regression model and Spearman rank correlation analysis were used to analyze the risk factors of AIP recurrence.Results During the follow-up period,19.19％(38/198)of AIP patients experienced a relapse.The 1-,3-,and 5-year cumulative recurrence rates were 6.57％,9.09％,and 12.63％,respectively,with type 1 AIP demonstrating a significantly higher recurrence rate than type 2 AIP(21.95％[36/164]vs 5.88％[2/34],P=0.030).Univariate logistic regression analysis showed that serum low density lipoprotein-cholesterol level(odds ratio[OR]=0.544,95％confidence interval[CI]0.321-0.924,P=0.024)and the duration of glucocorticoid maintenance therapy(OR=0.797,95％CI 0.704-0.902,P＜0.001)were the potential factors of AIP recurrence in 112 patients with definite data on the duration of glucocorticoid maintenance therapy.Multivariate logistic regression analysis showed that the duration of glucocorticoid maintenance therapy was independently associated with AIP recurrence(OR=0.813,95％CI 0.713-0.926,P=0.002).Spearman rank correlation analysis further demonstrated a negative correlation between the duration of glucocorticoid maintenance therapy and AIP recurrence(r=-0.545,P＜0.001).Additionally,receiver operating characteristic curve analysis indicated that the duration of glucocorticoid maintenance therapy had good predictive effect on AIP recurrence,with an area under curve value of 0.873(95％CI 0.800-0.945,P＜0.001).Conclusion Long-term regular glucocorticoid therapy is an independent protective factor against AIP recurrence,and it can significantly reduce the recurrence of AIP.

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

Macrophages are important immune cells involved in innate immunity,with significant heterogeneity and polarization.Macrophages can polarize into different phenotypes(mainly M1 and M2)under stimulation by various factors in the microenvironment,leading to different roles and functions.Macrophages play an important role in the pathophysiological mechanism of renal ischemia-reperfusion injury(RIRI).An excessive immune response will inevitably lead to tissue damage.M1 macrophages are pro-inflammatory cells involved in the clearance of pathogens,while M2-type macrophages have anti-inflammatory effects and participate in the repair and remodeling of renal tissue after RIRI.The balance between these macrophage phenotypes is thus an important factor affecting the outcome and treatment of RIRI.This review considers the pathophysiologic mechanism of macrophages in RIRI and the latest treatments from the perspective of macrophage polarization,with the aim of supporting further studies of the function of macrophage polarization in RIRI and adjusting the macrophage polarization process to improve RIRI treatment strategies.

OBJECTIVE To analyze the bacterial spectrum characteristics and drug resistance of midstream urine culture-positive cases in patients with urinary tract infection(UTI),and to provide reference for rational use of antibiotics.METHODS A retrospective analysis was conducted on 6 029 patients with urinary tract infections who had positive midstream urine cultures at the First Affiliated Hospital of Guangzhou Medical University from 2013 to 2023,with a total of 8 495 infectious bacterial detected,and the characteristics of the pathogens,antimicrobial susceptibility tests and the epidemiological features were analyzed.RESULTS There were 2 086 males and 3 943 fe-males.A total of 8 495 pathogens were isolated,of which 1 492 stains of gram-positive bacteria accounted for 17.56％,5 850 strains of gram-negative bacteria accounted for 68.86％,1 150 strains of fungi accounted for 13.54％,with Escherichia coli(42.30％),Klebsiella pneumoniae(7.59％),and Enterococcus faecalis(6.19％)being predominated.The major gram-negative bacteria had low resistance rates to meropenem,imipen-em and ertapenem(＜20％),and high resistance rates to ampicillin and cefazolin(＞34％).The major gram-posi-tive bacteria had low resistance rates to teicoplanin and quinupristin/dalfopristin(＜12％),very low resistance to linezolid(＜1％),and high resistance rates to erythromycin(＞40％).The main fungi had low resistance rates to flucytosine and amphotericin B(＜3％),while Candida tropicalis had high resistance rates to itraconazole,flu-conazole,and voriconazole(37.93％-42.18％).CONCLUSION The three most frequently isolated pathogens in the midstream urine cultures of patients with UTI are Escherichia coli,Klebsiella pneumoniae,and Group D En-terococcus faecalis,which show low resistance to tigecycline and high resistance to ciprofloxacin,ampicillin and levofloxacin,and these findings provide important references for clinical treatment of urinary tract infections.

Macrophages are important immune cells involved in innate immunity,with significant heterogeneity and polarization.Macrophages can polarize into different phenotypes(mainly M1 and M2)under stimulation by various factors in the microenvironment,leading to different roles and functions.Macrophages play an important role in the pathophysiological mechanism of renal ischemia-reperfusion injury(RIRI).An excessive immune response will inevitably lead to tissue damage.M1 macrophages are pro-inflammatory cells involved in the clearance of pathogens,while M2-type macrophages have anti-inflammatory effects and participate in the repair and remodeling of renal tissue after RIRI.The balance between these macrophage phenotypes is thus an important factor affecting the outcome and treatment of RIRI.This review considers the pathophysiologic mechanism of macrophages in RIRI and the latest treatments from the perspective of macrophage polarization,with the aim of supporting further studies of the function of macrophage polarization in RIRI and adjusting the macrophage polarization process to improve RIRI treatment strategies.

OBJECTIVE To analyze the bacterial spectrum characteristics and drug resistance of midstream urine culture-positive cases in patients with urinary tract infection(UTI),and to provide reference for rational use of antibiotics.METHODS A retrospective analysis was conducted on 6 029 patients with urinary tract infections who had positive midstream urine cultures at the First Affiliated Hospital of Guangzhou Medical University from 2013 to 2023,with a total of 8 495 infectious bacterial detected,and the characteristics of the pathogens,antimicrobial susceptibility tests and the epidemiological features were analyzed.RESULTS There were 2 086 males and 3 943 fe-males.A total of 8 495 pathogens were isolated,of which 1 492 stains of gram-positive bacteria accounted for 17.56％,5 850 strains of gram-negative bacteria accounted for 68.86％,1 150 strains of fungi accounted for 13.54％,with Escherichia coli(42.30％),Klebsiella pneumoniae(7.59％),and Enterococcus faecalis(6.19％)being predominated.The major gram-negative bacteria had low resistance rates to meropenem,imipen-em and ertapenem(＜20％),and high resistance rates to ampicillin and cefazolin(＞34％).The major gram-posi-tive bacteria had low resistance rates to teicoplanin and quinupristin/dalfopristin(＜12％),very low resistance to linezolid(＜1％),and high resistance rates to erythromycin(＞40％).The main fungi had low resistance rates to flucytosine and amphotericin B(＜3％),while Candida tropicalis had high resistance rates to itraconazole,flu-conazole,and voriconazole(37.93％-42.18％).CONCLUSION The three most frequently isolated pathogens in the midstream urine cultures of patients with UTI are Escherichia coli,Klebsiella pneumoniae,and Group D En-terococcus faecalis,which show low resistance to tigecycline and high resistance to ciprofloxacin,ampicillin and levofloxacin,and these findings provide important references for clinical treatment of urinary tract infections.

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions,expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet,a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment,and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass,food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions,PASI score,the value of transdermal water loss (TEWL),and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index,changes in the histopathological morphology of liver tissue under HE staining,changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR,and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group,the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P<0.001),significantly lower food intake (P<0.005),and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur,mental fatigue,etc. appeared. The TWEL were significantly increased(P<0.001),and the PASI scores also significantly increased(P<0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+neutrophil subpopulation,CD11binLy6Chigh monocyte subpopulation,CD11binCD11chigh classical dendritic cell subpopulation,F4/80-CD11c+dendritic cell subpopulation was significantly increased (P<0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration,and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P<0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated(P<0.005,P<0.001),while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P<0.05,P<0.01). ABCA1 protein level in skin increased(P>0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern,which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern.