Objective:To explore the effect and mechanism of different concentrations of metformin on bleomycin (BLM)-induced systemic sclerosis (SSc) mice model.Methods:C57BL/6 mice were divided into the normal group, the model group, the high, the medium and the low metformin (MET) treatment groups randomly. All mice were sacrificed after BLM and metformin treatment for 4 weeks. Local skin was exminedby histopathological staining method to measure the thickness of dermis and collagen, and immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and mRNA levels of Interleukin (IL)-17, forkhead box P3 (Foxp3) and α-smooth muscle actin (α-SMA). Flow cytometry was used to detect the percentage of effector T cell (Teff) and regulatory cells (Treg) in splenic mononuclear cells. The data such as dermal collagen thickness, α-SMA, IL-17, Foxp3, Teff and Treg levels were statistically analyzed by one-way analysis of variance. The data such as dermal collagen thickness, α-SMA, IL-17, Foxp3, Teff and Treg levels were analyzed by one-way analysis of variance, and least significant difference (LSD)- t or Kruskal-Wallis test was used for comparison between groups. Results:Compared with the normal group, remarkable fibrotic lesions appeared in the skin of mice in the model group, and the levels of T-helper cells (Th)1, Th2, Th17, and T follicular helper cells (Tfh) cells were increased, accompanied by a significant decrease in the level of Treg cells. After high-dose metformin treatment, the dermal thickness [(131±25) μm], collagen thickness [(119±18) μm], and α-SMA [(3.0±0.5)/HPH] were significantly reduced( F=14.390, P<0.01; F=40.245, P<0.01; F=44.626, P<0.01). Th1[(27.00±6.68)%], Th17[(0.56±0.20)%], Tfh[(6.4±1.6)%] cells ware significantlyreduced ( F=32.390, P<0.01; F=16.083, P<0.01; F=16.546, P<0.01), and Treg[(11.23±1.52)%] cells were significantly increased ( F=10.171, P<0.01). Conclusion:Metformin can effectively reverse the local skin changesin BLM-induced SSc mouse model, and show immune regulation and anti-fibrosis effects by restoring the Teff/Treg balance.

OBJECTIVETo investigate the quality of life of rectal cancer patients after anterior resection and the role of 5-hydroxytryptamine(5-HT) in the pathogenesis of anterior resection syndrome (ARS).

METHODSBetween November 2012 and October 2014, 90 rectal cancer patients who underwent Dixon procedure in the Institute of Surgery Research, Daping Hospital, Third Military Medical University, and developed ARS postoperatively were enrolled in the study. By clinic interview and telephone follow-up, they were investigated according to the 4 questionnaires, including gastrointestinal quality of life index(GIQLI), Wexner constipation and incontinence score(WCS, WIS), and 36-item short form health survey(SF-36). Associated clinical data and above parameters were compared between postoperative 0-6 months and 7-24 months. Expression of 5-HT in rectal mucosa was determined by immunohistochemistry preoperatively and postoperatively.

RESULTSThe GIQLI, WCS and WIS were significantly improved in 7-24 months group compared with those in 0-6 months group(all P<0.05). Furthermore, the SF-36 test result also showed significant improvement in the terms of physical function, physical role, vitality, social function, emotional role and health changes spheres in 7-24 months group(P<0.05). 5-HT expression in rectal mucosa(upper anastomosis 3402.95±1876.24, lower anastomosis 3045.35±1373.59 of ARS patients was significantly down-regulated compared with the preoperative expression(rectal margin mucosa 7176.60±3927.61)(P<0.05).

CONCLUSIONSPatients with ARS experience a significant trend toward recovery in their whole long-term quality of life. The down-regulation of 5-HT expression in rectal mucosa after surgery may be related with the pathogenesis of ARS.

Constipation ; Humans ; Intestinal Mucosa ; Prospective Studies ; Quality of Life ; Rectal Neoplasms ; Serotonin ; Treatment Outcome

Objective:To explore the expression level of interleukin-1 receptor-associated kinase-1 (IRAK1) in the peripheral blood of rheumatoid arthritis (RA) patients and analyze its relevance between disease activity and CD4 + T cell subsets. Methods:① The concentration of IRAK1 in the peripheral blood of 77 RA patients and 24 healthy controls were detected by enzyme linked immunosorbent assay (ELISA). ② The demo-graphic and clinical data of the RA group including disease activity score with 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CD4 + T cell subsets in peripheral blood. ③Independent sample t test or Mann-Whitney U test were used to compare the differences between the two groups. Spearman rank correlation test and multiple linear regression were used to analyze the correlation between IRAK1 expression level and clinical data. Results:① The IRAK1 level of the peripheral blood of RA patients was significantly higher than in the normal controls ( P<0.001). ② Compared to normal controls, the peripheral blood of the RA group, the absolute numbers and proportion of regulatory T (Treg) cells were decreased ( P<0.001), the absolute numbers and proportion of helper T (Th) 17 and the ratio of Th17/Treg were increased. Moreover, the ratio of Th17/Treg was also increased. ③ With the increase of disease activity in RA patients, the expression of IRAK1 also increased. The expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR, number of joints involved and DAS28, and had statistically significant difference between the two groups ( r=0.23, P<0.05; r=0.24, P<0.05; r=0.27, P<0.05). Meanwhile, it was sign-ificantly negatively correlated with the percentage of Treg ( r=-0.27, P<0.05), and was significantly positively correlated with the ratio of Th17/Treg ( r=0.23, P<0.05) . However, there was no significant correlation with the ratio of Th1/Th2( P>0.05). Furthermore, multiple stepwise regression analysis showed that the expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR and the number of joints involved ( β=0.34, P=0.019; β=0.27, P=0.004), and it was inversely correlated with percentage of Treg ( β=-0.23, P=0.047, R2=0.219). Conclusion:IRAK1 expression in the peripheral blood of RA patients is up-regulated and correlated with disease activity. The decrease of Treg and the imbalance of Th17/Treg caused by high expression of IRAK1 may be one of the main factors for the occurrence and development of RA. Interfering the expression of IRAK1 may be a potential new target for RA treatment.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.