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 network structure of anxiety,depression and sleep among individuals under long-term high-altitude exposure.Methods A total of 303 subjects who had resided at high altitudes for more than 6 months on end were selected.The insomnia severity index(ISI),patient health questionnaire(PHQ-9),and generalized anxiety disorder scale(GAD-7)were employed to assess insomnia,depression and anxiety before network analysis was conducted to identify the central and bridge nodes in the symptom network.Results The incidence of moderate or severe depression,anxiety and insomnia were 38.9％[95％confidence interval(CI):33.4％-44.5％],23.1％(95％CI:18.3％-27.9％),and 18.5％(95％CI:14.1％-22.9％),respectively."Noticeability of sleep problems by others"had the highest expected influence centrality,followed by"sleep maintenance""uncontrollable worry""restlessness"and"sleep problems".Five bridge symptoms were identified:"sad mood""sleep problems""restlessness""feeling afraid"and"trouble relaxing".Conclusion Sleep-related symptoms play a crucial role in the overall network structure,serving as both central and bridge nodes.Additionally,the"feeling down or depressed"acts as a bridge node and holds importance in the comorbidity network of anxiety and depression.Targeting these key symptoms through intervention and prevention strategies may improve the psychological well-being of individuals with long-term residence in high-altitude regions.

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.

Objectives:To investigate the clinical feasibility of three-dimensional(3D)high-resolution late gadolinium enhancement(LGE)MRI in accessing left atrial myocardial fibrosis in patients with atrial fibrillation(AF). Methods:A total of 34 AF patients referred for hybrid surgical ablation were retrospectively enrolled in this study.3D-LGE-MRI images were acquired by Siemens 3.0 T machine and analyzed by ADAS post-processing software by two experienced radiologists to obtain parameters such as the area and the area percentage of LGE.Regional analysis was performed by one of the two radiologists at ten left atrial segments.The Kappa test was used to assess the agreement for scoring image quality,and the interclass correlation coefficient(ICC)was used to evaluate the interobserver agreement of LGE parameters.The parameters of left atrial morphology,area(and area percentage)of LGE,and location of LGE were compared between patients with persistent AF and paroxysmal AF. Results:Images of all 34 patients were considered to have diagnostic value.The scores of the overall image quality and the clarity of the left atrial wall evaluated by two radiologists were(2.88±0.64)points and(3.26±0.75)points(radiologist 1),(2.97±0.58)points and(3.24±0.70)points(radiologist 2),respectively.The corresponding Kappa values were 0.724 and 0.859.Both the area and the area percentage of LGE showed good consistency among observers,and the ICCs were 0.969 and 0.950,respectively.The difference in the area of LGE and the area percentage of LGE between patients with paroxysmal and persistent atrial fibrillation was similar(both P＞0.05).Compared with patients with paroxysmal AF,patients with persistent AF had a higher Utah stage and more severe myocardial fibrosis in the right inferior pulmonary vein antrum and the left atrial septum(all P＜0.05). Conclusions:3D high-resolution LGE-MRI provides a non-invasive way to visualize and quantify left atrial myocardial fibrosis.The extent of left atrial fibrosis in patients with persistent AF is more severe than that in patients with paroxysmal AF,with a preferential distribution in the right inferior pulmonary vein antrum and the left atrial septum.

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 explore the clinical efficacy of immunoadsorption in highly sensitized kidney transplant (KT) candidates.Methods:From September 2019 to April 2023, the relevant clinical data were retrospectively reviewed for 26 highly sensitized KT recipients. Protein A immunoadsorption desensitization therapy was offered after KT. The effect of immunosorbent on reducing anti-human leukocyte antigen (HLA) antibodies was summarized. And operative success rate and postoperative complication incidence were calculated.Results:The mean number of treatment session was (10.76±5.53). The highest level of HLA-Ⅰ antibody mean fluorescence intensity (MFI) dropped from (17 921±4 442) to (7 333±6 434) with a decline of 59% and HLA-Ⅱ antibody MFI decreased from (21 135±5 245) to (10 989±7 627) with a decline of 48%. The differences were statistically significant (both P<0.001). All kidneys were harvested from cadavers. The complications were acute antibody mediated rejection (7 cases), perioperative pulmonary infection (3 cases) and myelosuppression (2 cases). The average follow-up period was (30.8±12.6) month. The graft survival rate was 88.5% (23/26) and the recipient survival rate 100% (26/26) . Conclusions:Immunoadsorption therapy can effectively reduce HLA antibody in highly sensitized KT candidates, thereby increasing the probability of successful KT. In terms of safety, immunosorbent therapy may boost the potential risks of infection and myelosuppression. It requires heightened attention.

With the continuous advancement of China′s deepening medical reform, the reform of the primary healthcare service system has gradually become an important issue in health work. In recent years, Yuhuan city, Zhejiang province has taken the people-centered integrated care mode as the theoretical basis, focused on the construction of integrated outpatient clinics, and carried out extensive and in-depth integrated medical system reform with a series of measures such as policy guidance, financial support and medical insurance assistance. After the implementation of the integrated reform, patient satisfaction has continued to improve, the level of health management has steadily increased, and residents′ willingness to seek medical treatment locally has significantly increased. This can provide reference for the construction of an integrated medical service system at the grassroots level.

Objective:To investigate the clinical results of decompression preserving proximal upper laminae combined with lumbar instrumental fusion in the treatment of lumbar degenerative diseases and the prevention of adjacent segment degeneration (ASD).Methods:A retrospective analysis was conducted on 124 patients (the reserved group) with lumbar degeneration who underwent compression preserving proximal upper laminae combined with fusion surgery involving upper half of the lamina, upper half of the spinous process, adjacent facets, and interspinous ligament at Nanjing Drum Tower Hospital between March 2018 and February 2020. These patients were followed up for more than 2 years. Additionally, 130 patients who underwent traditional total laminectomy decompression combined with fusion surgery from January 2016 to February 2018 were selected as the control group (total laminectomy group). In the reserved group, there were 60 males and 64 females, aged 58.3±10.3 years, including 50 cases of giant lumbar disc herniation, 11 cases of lumbar disc herniation with ossification, 10 cases of simple lumbar spinal stenosis, and 53 cases of degenerative lumbar spondylolisthesis. Total laminectomy group comprised 62 males and 68 females, aged 59.6±9.2 years, with 51 cases of giant lumbar disc herniation, 13 cases of lumbar disc herniation with ossification, 11 cases of simple lumbar spinal stenosis, and 55 cases of degenerative lumbar spondylolisthesis. The number of operative segments, operative time, intraoperative blood loss, postoperative hospital stay, complications, extent of laminectomy, dural sac area, and sagittal spinopelvic parameters were compared between the two groups. Fusion status, adjacent segment stability, and the incidence of ASD were assessed at the last follow-up. Oswestry disability index (ODI) and visual analogue scale (VAS) for back and leg were used to evaluate clinical effectiveness.Results:The follow-up time was 30.5±5.4 months in the reserved group and 31.0±5.8 months in total laminectomy group, and the difference was not statistically significant ( t=0.63, P=0.528). In patients undergoing single segment surgery, the operation time (173.6±47.3 min), blood loss (351.7±102.0 ml) and postoperative hospital stay (7.8±3.1 d) in the reserved group were lower than those in total laminectomy group (196.2±34.2 min, 401.9±97.2 ml, 9.9±3.6 d, respectively), and the differences were statistically significant ( t=2.93, P=0.004; t=2.69, P=0.008; t=3.26, P<0.001). The dural sac area in both groups was significantly improved after surgery, but the extent of laminectomy in the reserved group (22.8±4.5 mm) was smaller than that in total laminectomy group (29.5±4.8 mm), and the difference was statistically significant ( t=7.62, P<0.001). The above indicators of the patients with two segment or three segments in the reserved group were better than those in total resection group, with a statistically significant difference ( P<0.05). PI, PT, SS, and LL showed significant improvement in both groups compared to preoperative values ( P<0.05), with no statistically significant differences between the groups ( P>0.05). At the last follow-up, both groups achieved Bridwell I or II fusion level. The proportion of adjacent vertebral instability in the reserved group (11.3%, 14/124) was lower than that in total laminectomy group (22.3%, 29/130), and the difference was statistically significant (χ 2=5.48, P=0.019). The total incidence of ASD in the reserved group (20.9%, 26/124) was lower than that in total laminectomy group (36.2%, 47/130), and the difference was statistically significant (χ 2=7.15, P=0.008). R-ASD (16.9%, 21/124), S-ASD (4.0%, 5/124) and O-ASD (0, 0/124) in the reserved group were lower than those in total laminectomy group [(25.4% (33/130), 9.3% (12/130) and 1.5% (2/130), respectively)], and the difference was statistically significant (χ 2=8.20, P=0.027). ODI and VAS of back and leg were significantly reduced in both groups compared to preoperative values, and the differences were statistically significant ( P<0.05). There were no significant differences in ODI and VAS scores of back and leg in the reserved group compared with total laminectomy group at 3 months, 1 year, and the last follow-up ( P>0.05). Conclusion:Decompression with preservation of the upper half of the lamina can reduce intraoperative blood loss, shorten operation time and postoperative hospital stay, achieve comparable decompression effects to traditional decompression surgery, and effectively reduce the occurrence of adjacent segment instability and ASD.

Humans ; Bradycardia/therapy* ; Tricuspid Valve Insufficiency ; Pacemaker, Artificial/adverse effects* ; Cardiac Pacing, Artificial