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.

AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.

Objective:To explore the risk factors of acute kidney injury(AKI)after liver transplantation(LT), examine its prognostic impact and construct a clinical prediction model.Methods:Clinical data are retrospectively reviewed for 220 LT recipients.They are divided into two groups of AKI(93 cases)and non-AKI(127 cases)according to the occurrence of AKI post-LT.Clinical data of two groups are compared.The variables with statistically significant inter-group differences in univariate analysis are included for multivariate analysis for obtaining the independent risk factors for AKI post-LT.Then the independent risk factors are employed for fitting a prediction model and a visual nomogram is constructed.At the same time, discrimination and calibration of the prediction model are evaluated.Extubation time, length of intensive care unit(ICU)stay, continuous renal replacement therapy(CRRT)rate, length of hospital stay, in-hospital mortality, estimated glomerular filtration rate(eGFR)at discharge, incidence of chronic renal failure(CRF)and readmission times are compared between two groups.Survival analysis is also performed between AKI and non-AKI groups and AKI 0/1 and AKI 2/3 stages.Results:The incidence of AKI post-LT is 42.3%.Age( OR=1.036, 95% CI: 1.001~1.073), preoperative serum creatinine level( OR=1.030, 95% CI: 1.011~1.049), platelet count( OR=0.992, 95% CI: 0.985~0.999), Child-Pugh class C( OR=2.678, 95% CI: 1.031~6.952), postoperative abdominal infection( OR=2.271, 95% CI: 1.120~4.603)and abdominal hemorrhage( OR=3.869, 95% CI: 1.016~14.72)are independent risk factors for AKI post-LT.The AUC/C-index of nomogram prediction model is 0.789 with a Brier score of 0.183, showing decent discrimination and calibration.According to the nomogram score, the recipients with a risk of AKI>50% are included into high-risk group while those with a risk of AKI<50% into low-risk group.Postoperative survival of low-risk group is better than that of high-risk group( P<0.001).Compared with non-AKI group, AKI group had a later extubation time( P=0.003), a longer length of ICU stay( P<0.001)and hospital stay( P=0.001), a higher rate of CRRT usage( P<0.001)and in-hospital mortality( P<0.001), a lower eGFR at discharge( P<0.001)and a higher incidence of CRF( P<0.001).Postoperative survival of non-AKI group was better than that of AKI group( P=0.048).Postoperative survival of patients with AKI 0/1 is better than that of those with AKI 2/3( P=0.002). Conclusions:Advanced age, high preoperative serum creatinine, low preoperative platelet, poor preoperative liver function, postoperative abdominal infection and abdominal hemorrhage may elevate the risks of AKI post-LT.And the nomogram prediction model based upon the above risk factors has a high value of clinical application.

ObjectiveTo observe the effect of neuromuscular training on femoroacetabular impingement. MethodsFrom January, 2017 to November, 2021, 27 patients with femoroacetabular impingement in Beijing Rehabilitation Hospital were randomly divided into control group (n = 13) and observation group (n = 14). The control group accepted routine rehabilitation training, and the observation group accpeted neuromuscular training in addition. They were assessed with Visual Analogue Scale (VAS) for pain, peak torque (PT) of hip flexion and extension, Y-balance test (YBT) and simplified International Hip Outcome Tool (iHOT-12) before and after treatment. ResultsThe VAS score, PT, YBT score and iHOT-12 score improved in the observation group after treatment (|t| > 3.628, P < 0.01), while the VAS score and PT improved in the control group (|t| > 3.409, P < 0.01). After treatment, the VAS score, PT, YBT score and iHOT-12 score were better in the observation group than in the control group (|t| > 2.067, P < 0.05). ConclusionNeuromuscular training can relieve the pain of patients with femoroacetabular impingement, and improve the muscle strength and function of hip joint.

ObjectiveTo explore the effect of trunk control training during unstable sitting on knee pain and function in patients with patellofemoral pain syndrome. MethodsFrom January, 2019 to December, 2021, 41 patients with patellofemoral pain syndrome in Beijing Rehabilitation Hospital were randomly divided into control group (n = 20) and experiment group (n = 21). Both groups accepted routine rehabilitation, and the experiment group accepted trunk control training during unstable sitting in addition, for four weeks. They were assessed with Visual Analogue Scale for pain (VAS) and Anterior Knee Pain Scale (AKPS), and measured stability indexes with Balancer before and after treatment. ResultsAll the VAS score, AKPS score, and the overall, anterior-posterior and left-right stability indexes improved in both groups after treatment (|t| > 12.089, P < 0.001); and improved more in the experiment group than in the control group (|t| > 5.864, P < 0.001). ConclusionTrunk control training during unstable sitting may improve knee pain and function, and motor control.

Objective: To quantitatively assess biochemical alterations in the cartilage of the subtalar and midtarsal joints in chronic lateral ankle instability (CLAI) patients with isolated anterior talofibular ligament (ATFL) injuries and combined calcaneofibular ligament (CFL) injuries using MRI T2 mapping. Materials and Methods: This study was performed according to regulations of the Committee for Human Research at our institution, and written informed consent was obtained from all participants. Forty CLAI patients (26 with isolated ATFL injuries and 14 with combined ATFL and CFL injuries) and 25 healthy subjects were recruited for this study. All participants underwent MRI scans with T2 mapping. Patients were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system. The subtalar and midtarsal joints were segmented into 14 cartilage subregions. The T2 value of each subregion was measured from T2 mapping images. Data were analyzed with ANOVA, the Student’s t test, and Pearson’s correlation coefficient. Results: T2 values of most subregions of the subtalar joint and the calcaneal facet of the calcaneocuboid joint in CLAI patients with combined CFL injuries were higher than those in healthy controls (all p < 0.05). However, there were no significant differences in T2 values in subtalar and midtarsal joints between patients with isolated ATFL injuries and healthy controls (all p > 0.05). Moreover, T2 values of the medial talar subregions of the posterior subtalar joint in patients with combined CFL injuries showed negative correlations with the AOFAS scores (r = -0.687, p = 0.007; r = -0.609, p = 0.021, respectively). Conclusion CLAI with combined CFL injuries can lead to cartilage degeneration in subtalar and calcaneocuboid joints, while an isolated ATFL injury might not have a significant impact on the cartilage in these joints.

OBJECTIVETo observe the clinical efficacy difference among elongated needle, filiform needle and medication for post-stroke indigestion.

METHODSSixty cases of post-stroke indigestion were randomly assigned into an elongated needle group, a filiform needle group and a medication group, 20 cases in each one. Acupuncture of restoring consciousness and inducing resuscitation and conventional medical treatment were applied in the three groups. 125 mm elongated needles were perpendicularly inserted at Zhongwan (CV 12), Liangmen (ST 21) and Tianshu (ST 25) in the elongated needle group; 20 to 30 mm perpendicular filiform at the same points in the filiform needle group. All the treatment was given for 4 weeks, 6 times a week, 1 time a day. Domperidone was prescribed orally in the medication group for 4 weeks, 3 times a day and once 10 mg. The indexes were dyspepsia TCM symptom score, Liz dyspepsia questionnaire (LDQ), Nepean Dyspepsia Index of quality of life (NDLQI), Safety Data Sheet (SDS) self rating scale and side effect scale (TESS). The effects were evaluated.

RESULTSThe scores of TCM symptom, LDQ, SDS scores in the three groups decreased and NDLQI increased after 7-day, 14-day, and 28-day treatment as compared with those before treatment (<0.05,<0.01). The TCM symptom score and LDQ score in the elongated needle group after 28-day treatment were lower than those in the filiform needle and medication groups (<0.05,<0.01). The SDS score in the medication group was lower than that in the elongated needle and filiform needle group (both<0.05). There were no significant statistical difference for NDLQI score in the three groups (>0.05). The total effective rate was 90% (18/20) in the elongated needle group; those in the filiform needle group and medication group were 70% (14/20) and 75% (15/20) respectively, indicating statistical significance (<0.01).

CONCLUSIONAcupuncture with elongated needle can obviously improve symptoms in the patients with post-stroke indigestion, which is better than filiform needle and medication.

Objective To investigate the lead and cadmium contents in different sampling sites from full term neonatal placenta and to explore the role of placental sample in the evaluation of intrauterine heavy metals exposure.Methods The placentas from 30 healthy full term neonates were collected from the West China Second Hospital of Sichuan University during May and June 2016.Each placenta fetal side was divided into the left and right parts with the umbilical vein in the umbilical cord cross-section as the 12 o'clock direction.The villus lobular tissue samples were taken from the 1/4 radius in left part (site A) and 3/4 radius in the right part (site B).The graphite furnace atomic absorption spectrometry was used to detect the lead and cadmium contents in the samples.The elements contents in the site A and B were performed the paired t-test and correlation analysis.Results The mean contents of lead and cadmium in dry weight sample at placental site A were 91.8 and 66.7μg/kg which at the site B were 88.9 and 64.8 μg/kg respectively.The lead and cadmium contents at these two sites presented the positive correlation,the coefficients were 0.98 and 0.97 respectively,whereas the difference in contents between the tissues from different placental sites had no statistical significance.Conclusion The lead and cadmium contents of villus lobular tissue in the central part of placenta fetal side (1/4-3/4 radius area) are basically consistent,which is a reliable indicator for evaluating the intrauterine heavy metals exposure.

The aging of population and the increasingly morbidity rate of chronic disease had brought great influence on public health and economy.And community whose scientific management model could improve effectivity was a main prevention place for chronic disease.Thus on the basis of domestic and foreign literatures,several types of chronic disease community management models were introduced,and aimed at providing a reference for community chronic disease management.