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.

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

Pyroptosis is a programmed cell death mediated by cysteine proteases and is characterized by mitochondrial participation,inflammasome assembly,plasma membrane perforation,and inflammatory release.As an important mechanism mediating the body's inflammatory responses,pyroptosis plays a key role in renal ischemia-reperfusion injury(RIRI).This article reviews the molecular mechanisms of pyroptosis,pyroptotic mechanisms in RIRI,and the progress of research into therapeutic drugs in recent years,with the aim of providing a theoretical reference for the development of early treatments for RIRI.

Background::The serum vitamin D level varies widely by population, and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus (T2DM). However, the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is unclear. The study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and the risk of T2DM and evaluated whether the association is modified by genetic predisposition.Methods::In the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cohort, 1862 participants free of T2DM at baseline were included. A weighted genetic risk score was calculated with 28 variants associated with T2DM. Hierarchical logistic models were used to examine the association of serum 25(OH)D and genetic risk with T2DM.Results::After a 5-year follow-up, 132 cases of T2DM were documented. We observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment (χ 2 = 0.571, Pfor trend = 0.426). Compared to those in the lowest quartile of 25(OH)D, the odds ratios (ORs) (95% confidence interval [CI]) for participants with increased quartiles were 1.29 (0.74-2.25), 1.35 (0.77-2.36), and 1.27 (0.72-2.24), respectively. We observed a positive association of glycated hemoglobin (HbA1c) with 25(OH)D at baseline (β = 1.752, P = 0.001) and after follow-up (β = 1.385, P = 0.003), and a negative association of ln conversion homeostasis model assessment (HOMA)-β with 25(OH)D at baseline (β = -0.982, P = 0.021). There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM (χ 2 = 2.710, Pfor interaction = 0.100). The lowest OR (95% CI) of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D (0.17 [0.05–0.62]). Conclusion::Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

Pancreatic cystic neoplasm(PCN)is a category of pancreatic tumors with significant heterogeneity.In recent years,the detection rate of PCN has been increasing,and it has gradually become a concern of clinicians.Endoscopic ultrasound(EUS)can be close to the pancreas for scanning and biopsy,and it has certain advantages in the diagnosis and treatment of PCN.This review mainly summarizes the latest progress of EUS in the diagnosis and treatment of PCN.Cyst fluid molecular markers,such as Kirsten rat sarcoma viral oncogene homolog,GNAS complex locus,Von Hippel-Lindau tumor suppressor gene,as well as emerging endoscopic technologies such as EUS-guided needle based confocal laser endomicroscopy and through-the-needle biopsy,have all showed the potential to significantly improve the diagnostic accuracy of PCN.EUS-guided ablation is an emerging minimally invasive treatment technique for PCN,with the efficacy and safety of chemical ablation being supported by a substantial amount of research.

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.

Objective:To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC).Methods:Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups.Results:The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2=6.247, P=0.012). Conclusion:EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Objective:To compare the early clinical outcomes, screw placement accuracy and supradjacent facet joint violation between O-arm navigated minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and TLIF for the treatment of lumbar spondylolisthesis.Methods:We retrospectively reviewed a cohort of low-grade single level lumbar spondylolisthesis patients who have received O-arm navigated MIS-TLIF or open-TLIF treatment from May 2018 to July 2023. There were 60 patients in MIS-TLIF group including 24 males and 36 females, and the average age was 41.0±13.9 years (18-73 years). There were 120 patients in open-TLIF group including 43 males and 77 females, and the average age was 41.6±12.6 years (18-69 years). The demographic and perioperative data of patients were recorded. Preoperative lumbar CT and MRI were evaluated to assess the grade of adjacent facet joint degeneration and fatty infiltration in the lumbar paraspinal muscles. The slip parameters were measured by lateral X-ray films before and after operation, and the screw placement accuracy and supradjacent facet joint violation were evaluated by postoperative CT. Patient reported outcomes, including Oswestry disability index (ODI) and visual analogue scale (VAS) were collected preoperatively and 3 months postoperatively.Results:There was no significant difference in demographic data, adjacent facet joint degeneration, fatty infiltration of lumbar paraspinal muscles and preoperative ODI and VAS scores between the two groups ( P>0.05). The operation time in MIS-TLIF group (223.3±23.0 min) was significantly longer than that in open-TLIF group (187.0±30.5 min, t=8.130, P<0.001), while the intraoperative blood loss (150.7±56.8 ml vs. 392.8±161.5 ml, t=-11.253, P<0.001), postoperative drainage (60.4±19.8 ml vs. 215.2±57.2 ml, t=-20.328, P<0.001) and postoperative hospital stay (4.5±1.7 d vs. 8.4±2.5 d, t=-10.769, P<0.001) in MIS-TLIF group were significantly less. The 3-month postoperative VAS back pain of the MIS-TLIF group (2.0±1.7) was lower than the open-TLIF group (3.2±2.0, t=-3.956, P<0.001). Both groups had similar slip reduction results ( P>0.05). The accuracy of the pedicle screw placement in MIS-TLIF group (98.8%) was better than open-TLIF group (92.3%, P<0.001). The incidence of supradjacent facet joint violation in the MIS-TLIF group was lower than open-TLIF group (27.5% vs. 51.7%, χ 2=19.111, P<0.001). There were no notable surgical complications in MIS-TLIF group except temporary submuscular hematoma in one patient. In open-TLIF group, dural tear occurred in three patients intraoperatively, one patient experienced transient L 5 nerve root palsy after surgery and one patient had wound superficial tissue infection. All the complications were successfully treated with conservative measures. Conclusion:O-arm navigated MIS-TLIF had better short-term clinical effect and higher accuracy of pedicle screw placement in treating lumbar spondylolisthesis.

Objective:To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC).Methods:Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups.Results:The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2=6.247, P=0.012). Conclusion:EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Objective To evaluate the effect of negative-pressure wound therapy with irrigation(NPWTi)combined with red and blue light on diabetic foot wounds.Methods According to random number method,a total of 80 patients with type 2diabetes combined with diabetic foot admitted to Xuzhou Central Hospital from December 2021 to May 2022 were selected and divided into two groups:con-trol group and NPWTi + red and blue light group,with 40 cases in each group.All patients received basic treatment,while the control group received NPWTi treatment,NPWTi + red and blue light group was treated with red and blue light on the basis of NPWTi.The chan-ges of wound healing speed rate,serum inflammatory markers[erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),pro-calcitonin(PCT)]and growth factors[vascular endothelial growth factor(VEGF),epidermal growth factor(EGF),basic fibroblast growth factor(bFGF)]were observed before and 7days after treatment.After 12 weeks of follow-up,the wound healing rate of the two groups were observed,and the cumulative wound healing rate of the two groups was evaluated through Kaplan-Meier curve.Results Af-ter 7days of treatment,the wound healing rate of NPWTi + red and blue light group was faster than that of the control group(P<0.01).The average levels of VEGF,EGF and bFGF in NPWTi + red blue light group were higher than those in the control group(P<0.05),while the average levels of ESR,CRP and,PCT in NPWTi + red and blue light group were lower than those in the control group(P<0.05).The wound healing rate of NPWTi + red and blue light group at 12 weeks was higher than that of the control group(P<0.05).Kaplan-Meier curve analysis showed that the cumulative wound healing rate of NPWTi + red and blue light group was higher than that of the control group(P<0.05).Conclusion NPWTi combined with red and blue light is effective in treating diabetic foot wounds,and it is worthy of clinical application.