To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Psoriasis is a common immune-mediated inflammatory skin disease with multiple genetic and environmental risk factors.Abnormal vascular hyperplasia,excessive proliferation of keratinocytes and infiltration of various immune cells are the main pathological features.MAPK signaling pathway is involved in the pathogenesis of psoriasis,and SPRED1 has been proved to be a ma-jor negative regulator of MAPK signaling pathway in many diseases.This article reviews the possible role of SPRED1 in the pathogene-sis of psoriasis,in order to provide new insights into the pathogenesis of psoriasis and new directions for the treatment.

Female ; Infant, Newborn ; Humans ; Pregnancy ; Premature Birth ; Retrospective Studies ; Risk Factors ; Cerclage, Cervical ; Cervix Uteri

OBJECTIVE To investigate the effect of vitamin D receptor(VDR) genetic polymorphism on the concentration of tacrolimus in renal transplant recipients at early stage after transplantation.METHODS The 360 cases of renal transplant recipients who received tacrolimus, mycophenolic acid, and glucocorticoid were recruited. CYP3A5(rs776746) and VDR(VDR ApaI rs7975232, VDR BsmI rs1544410, VDR FokI rs2228570 and VDR TaqI rs731236) genotypes were determined. The differences of concentration(C), dose(D) and the ratio of concentration to dose(C/D) of tacrolimus were compared among all of the genotype groups at the seventh day after renal transplantation. RESULTS The C and C/D of tacrolimus in CYP3A5 non-expresser(GG genotype) were all significantly higher than CYP3A5 expresser(AA and AG genotype)(P<0.05). When taking the different CYP3A5 genotypes in consideration, it was found that the C/D in patients with VDR ApaI rs7975232 AA genotype was significantly lower than those with AC and CC genotypes for CYP3A5 non-expresser(P<0.05). However, VDR ApaI rs7975232 gene polymorphism had no influence on C and C/D of tacrolimus in CYP3A5 expresser. Besides, no matter in CYP3A5 expresser or in non-expresser, VDR BsmI rs1544410, VDR TaqI rs731236 and VDR FokI rs2228570 had no effect on C, D and C/D of tacrolimus. CONCLUSION During the early stage of renal transplantation, the polymorphism of VDR ApaI rs7975232 show significant relevance with tacrolimus concentration in CYP3A5 non-expresser. The detection of the genotype might be helpful to guide individual therapy.

Background and Objectives: Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis. Methods: and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3. Conclusions We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.

Astragali radix(AR,the dried root of Astragalus)is a popular herbal remedy in both China and the United States.The commercially available AR is commonly classified into premium graded(PG)and ungraded(UG)ones only according to the appearance.To uncover novel sensitive and specific markers for AR grading,we took the integrated mass spectrometry-based untargeted and targeted metabolomics ap-proaches to characterize chemical features of PG and UG samples in a discovery set(n=16 batches).A series of five differential compounds were screened out by univariate statistical analysis,including arginine,calycosin,ononin,formononetin,and astragaloside Ⅳ,most of which were observed to be accumulated in PG samples except for astragaloside Ⅳ.Then,we performed machine learning on the quantification data of five compounds and constructed a logistic regression prediction model.Finally,the external validation in an independent validation set of AR(n=20 batches)verified that the five com-pounds,as well as the model,had strong capability to distinguish the two grades of AR,with the pre-diction accuracy＞90％.Our findings present a panel of meaningful candidate markers that would significantly catalyze the innovation in AR grading.

To explore the effect of Astragalus membranaceus, a traditional Chinese medicine, on metabolic homeostasis of heart, brain and blood in mice, and to elucidate the cardio-cerebrovascular protective mechanisms of AR from the perspective of metabolic regulation. Thirteen ICR male mice were randomly divided into two groups which were intragastrically administered with ultrapure water and aqueous extract of Astragalus membranaceus for 10 consecutive days, respectively. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to comprehensively characterize the metabolic profiles of serum, heart and brain tissues. Multivariate statistical analysis combined with nonparametric tests were applied to screen and identify different metabolites, and then the related metabolic pathways were uncovered. Multivariate statistical analysis showed that the metabolic profiles of serum, heart, and brain tissues of mice after Astragalus membranaceus intervention significantly changed compared with the control group. A total of 15, 19, and 17 metabolites were identified in serum, heart, and brain tissues, respectively, among which palmitic acid and LysoPC (20∶3) were screened out from all types of biological samples. The results of metabolic pathway enrichment analysis showed that amino acid metabolism, phospholipid metabolism, fatty acid metabolism and tricarboxylic acid cycle were significantly affected. Astragalus membranaceus may protect the cardio-cerebrovascular system by regulating the metabolic homeostasis of amino acids, lipids and energy.

Objective: To explore the effect of high mobility group box-1 protein (HMGB1) on the balance of Th17/Treg in patients with immune thrombocytopenia (ITP). Methods: A total of 30 patients who were first diagnosed as ITP in the Fifth People's Hospital of Datong from July 2017 to April 2018 were selected as the case group, and another 30 healthy volunteers in the corresponding period were taken as the control group. The proportion of Th17 and Treg cells was detected by using flow cytometry, and the concentration of HMGB1, interleukin (IL)-17 and transforming growth factor β (TGF-β) in plasma was tested by using enzyme-linked immunosorbent assay (ELISA). Isolated peripheral blood mononuclear cells (PBMC) were cultured in vitro. After the treatment with recombinant human HMGB1 (rhHMGB1), real-time polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression changes in Treg cell transcription factor intracellular forkhead helix transcription factor 3 (Foxp3) and Th17 cell transcription factor retinoid related orphan receptor γt (RORγt). The differences of indicators in Treg cell transcription factor peripheral blood between the case group and the control group were compared, and the balance correlation between HMGB1 and Th17/Treg was analyzed. Results: Compared with the healthy control group, the proportion of Th17 cells and the expression level of HMGB1 and IL-17 in peripheral blood of ITP patients were increased (all P < 0.01), while the proportion of Treg cells and the level of TGF-β were decreased (all P < 0.01). The proportion of Th17 cells and the expression level of IL-17 and HMGB1 in peripheral blood of ITP patients were positively correlated with the concentration of HMGB1 (all P < 0.01); the proportion of Treg cells and the level of TGF-β were negatively correlated with the expression level of HMGB1 (all P < 0.01). In vitro experiments, the expression of intracellular RORγt mRNA was increased compared with the negative control group (1.50±0.24 vs. 0.93±0.22, t = 9.612, P < 0.01), and the expression of Foxp3 mRNA was decreased compared with the negative control group after the stimulation of PBMC by rhHMGB1 (0.72±0.19 vs. 1.08±0.18, t = 7.387, P < 0.01). Conclusion The high level of HMGB1 in the peripheral blood of ITP patients induces Th17/Treg imbalance and aggravates inflammatory reactions, which may be an important cause of ITP.

OBJECTIVE： To study the effects of ethanol extract of Sanguis Draconis on the survival of perforating flap model in rats and PI3K/Akt/eNOS pathway. METHODS： Perforating flap model was established by cutting off surrounding vessels and keeping one perforator. After modeling， the rats were divided into model group （external use， normal saline） and ethanol extract of Sanguis Draconis （EESD， the content of dracorhodin was 75.08 mg/g） group （external use， 0.21 g/cm2）， with 10 rats in each group. They were given relevant medicine for consecutive 7 days， once a day. The flap survival rate and flap microvessel density were determined after given relevant medicine 7 days. Human umbilical vein endothelial cells （HUVECs） were reoxygenated and glycoconjugated 16 h after hypoxia and hypoglycemia to establish oxygen-glucose deprivation/oxygen-glucose recovery model of HUVECs. After modeling， model cells were divided into normal group， model group， dracorhodin high-concentration， medium- concentration and high-concentration groups （2.5， 1.0， 0.5 μg/mL）. After reoxygenated and glycoconjugated for 24 h， cells morphology was observed by microscope； cell viability and the content of NO were detected by MTT assay and colorimetry. mRNA expression of Akt， PI3K and eNOS， PI3K protein expression， the phosphorylation of Akt and eNOS protein were determined by RT-PCR and Western blot assay. RESULTS： In rat experiment， compared with model group， flap survival rate and microvessel density of rats were increased significantly in EESD group （P＜0.01）. In cell experiment， compared with normal group， the survival rate of HUVEC， NO content， mRNA expression of PI3K， Akt， eNOS，PI3K protein expression， the phosphorylation of Akt and eNOS protein were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， dracorhodin high-concentration， medium-concentration and high-concentration groups survival rate of HUVEC cells， NO content， mRNA expression of PI3K， Akt and eNOS， PI3K protein expression， the phosphorylation of Akt and eNOS protein were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： The survival rate of perforating flap model in rat can be increased by treating with EESD， the mechanism of which may be associated with the activation of PI3K/Akt/eNOS pathway to protect endothelial cells.

OBJECTIVETo observe the role of myeloperoxidase(MPO)and eosinophilic cationic protein(ECP)in the airway inflammation and their correlation with clinical feature in asthma-COPD overlap (ACO) patients.

METHODSTwenty patients with COPD, 20 with asthma, 20 with ACO and 20 control subjects underwent pulmonary function test for measurement of forced expiratory volume in 1 second (FEV), forced vital capacity (FVC), peak expiratory flow (PEF), and maximum midexpiratory flow (MMF). COPD assessment test (CAT) was used to evaluate the clinical symptoms of the patients with COPD and ACO. The asthma control test (ACT) was used to evaluate the asthma control in the patients with asthma and ACO. Induced sputum samples were collected from the subjects for analysis of neutrophil and eosinophil ratios, and enzyme-linked immunosorbent assay was used to determine the expression levels of MPO and ECP in the sputum.

RESULTSNo significant difference was observed in the CAT scores between ACO group and COPD group (> 0.05). Compared with the asthma group, the patients with ACO had significantly lower ACT scores and lower FEV, PEF and MMF ( < 0.05). The patients with ACO had significantly higher FVC and sputum eosinophil ratio than those with COPD ( < 0.05), and a higher sputum neutrophil ratio than those with asthma ( < 0.01). In ACO group, the MPO level in sputum was significantly higher than that in the asthma group ( < 0.05), while sputum ECP level was significantly higher than that in both the asthma group and COPD group ( < 0.05 or 0.01). In ACO group, sputum MPO level was positively correlated with sputum neutrophil ratio (=0.8358, < 0.01) but was not correlated with CAT score or FEV (> 0.05); sputum ECP level was positively correlated with sputum eosinophil ratio (=0.4666, < 0.05) and was inversely correlated with ACT score (=-0.4966, < 0.05) and FEV (=-0.4610, < 0.05).

CONCLUSIONSBoth neutrophilic and eosinophilic inflammations occur in the airway of patients with ACO, and their sputum ECP level is negatively correlated with asthma control and obstructive airflow limitation.