OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

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.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective: To observe the alteration of brain glucose metabolic network in patients with somatoform disorders (SFD). Methods: ¹⁸F-fluorodeoxyglucose (FDG) PET images of 18 SFD patients (10 males, 8 females; age: (39.5±12.0) years; illness duration: (3.67±3.20) years) and 21 matched healthy controls (13 males, 8 females; age: (43.9±8.4) years) in Huashan Hospital of Fudan University from October 2011 to December 2012 were enrolled to construct the brain glucose metabolic networks for 2 groups (SFD group, control group) respectively. Then the global network properties (normalized clustering coefficient, normalized shortest path length, small-worldness and global efficiency) and local parameters (clustering coefficient and betweenness centrality of the node) were calculated using the graph theory. Differences between 2 groups were compared by permutation test with 1 000 permutations. The top 20% (18/90) were classified as Hub nodes based on the results of clustering coefficient and betweenness centrality of the node. Results: Small-worldness of SFD patients was similar to that of healthy controls (σ>1). There were decreased tendency in normalized clustering coefficient and global efficiency, and increased tendency in normalized shortest path length in SFD patients, but without significant differences (P>0.05). Compared to healthy controls, the betweenness centrality of left pallidum, left amygdala, left precuneus and right angular gyrus increased (permutation test, P<0.05); the betweenness centrality of left middle temporal gyrus, right superior occipital gyrus decreased (permutation test, P<0.05); the clustering coefficients of bilateral pallidum, bilateral thalamus, and left amygdala decreased (permutation test, P<0.05). Most changed Hub nodes (16/24) belonged to limbic system. Conclusion The changes of topological properties of brain glucose metabolic network in SFD patients including the decreased tendency of small-worldness and global efficiency, as well as the altered Hub nodes, may provide valid imaging evidences for brain dysfunction of somatization symptoms.

Objective To investigate the expression of programmed death receptor-1 (PD-1) in CD8+ T cells and FoxP3+CD4+ cells in patients with primary biliary cholangitis (PBC).Methods The peripheral blood and clinical data of 69 PBC patients in Peking Union Medical College Hospital and 58 health controls (HC) were collected.They were divided into initial treatment group and follow-up group according to whether they were treated or not.Patients in the treatment group were further divided into the refractory group and stable group according to treatment response.Flow cytometry was used to detect the expression of PD-1 in CDS+T cells and FoxP3+CD4+ cells.T-test and Person correlation analysis were used for data analysis.Results The PD-1 expression in peripheral blood mononuclear cells (PBMCs) of 69 PBC patients (12±9)％ was lower than that of HC (20±12)％ (t=-3.687,P＜0.01).The percentage of PD-1+ in FoxP3+ CD4+T cells was significantly increased in PBC (5.6±3.7)％ than HC (7.4±2.4)％ (t=2.048,P＜0.01).The proportion of CD8+T cells,PD-1 expression in CD8+T cells and the proportion of FoxP3+CD4+ cells weren't correlated with clinical parameters (P＞0.05).There was a negative correlation between the expression of PD-1 cells in FoxP3+CD4+ cells and GLOBE score (r=-0.307,P＜0.05).Conclusion The expression of PD-1 in peripheral CD8+T lymphocytes of PBC patients is lower than that of HC,and decreases more significantly in the refractory group.The expression of PD-1 on FoxP3+CD4+T cells is higher than that in HC,and is negatively correlated with the prognostic GLOBE score.It suggests that PD-1/PD-L1 pathway participates in the immune mechanism of PBC.

Objective To investigate the health related quality of life score [primary biliary cholangitis (PBC)-40] in patients with PBC,and the relationship between PBC-40 and clinical presentations.Methods The PBC-40 score and clinical presentations in PBC patients (n=65) were adapted in this study.Patients were divided into the untreated group and the treated group,and the treated group was further divided into ursodesoxycholic acid (UDCA) response group and UDCA non-response group.PBC-40 scores of different groups were analyzed by t-test and the relationship between PBC-40 and clinical presentations were analyzed with Pearson's test.Results Dimensions of PBC-40 scores of this group of patients were as follows:symptoms were (15.8±4.1) points,itch was (4.9±2.8) points,atigue was (23.8±8.9) points,cognitive dysfunction score was (11.4±4.7) points,social activity score was (17.0±7.5) points,and the emotion score was (6.5±3.1) points.The untreated group had higher emotion scores than the treated group (t=2.024,P=0.045).Compared with the UDCA response group,UDCA non-response group had higher scores in cognitive,social and emotion dimension (t =2.126,2.309,2.062,respectively,P=0.039,0.025,0.045,respectively).Itch score was significantly correlated with total bilirubin (TBil),direct bilirubin (DBil),alkaline phosphatase (ALP) and total bile acid (TBA) (r=0.349,0.345,0.324,0.427,respectively,P＜0.01),while the social scores were correlated with TBil,DBil,aspartate aminotransferase (AST) and TBA (r=0.361,0.383,0.316,0.331,P＜0.01) and emotion scores were associated with ALT,TBil,GGT,ALP,AST and TBA (r=0.332,0.430,0.265,0.326,0.297,0.353,P＜0.05).ConclusionPBC-40 can be used as a health-related quality of life assessment for PBC patients inChinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health quality of life in PBC patients.Conclusion PBC-40 can be used as a health-related quality of life assessment for PBC patients in Chinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health related quality of life in PBC patients.

Objective: To analyze the clinical features of dyslipidemia in patients with primary biliary cholangitis (PBC). Methods: The clinical and laboratory data of 136 PBC patients in Peking Union Medical College Hospital from 2010 to 2016 were retrospectively analyzed.The liver function was compared between patients with normal and abnormal blood lipids. Results: Among 136 PBC patients, 100(74%)had abnormal serum lipids. The incidence of increased cholesterol, low-density lipoprotein and triglyceride was 61%(59/96), 58%(48/83) and 47%(46/97), respectively; while that of reduced HDL-C was 26%(21/82). The incidences of pruritus [26%(26/100) vs. 8%(3/36), χ²=4.93, P=0.032], serum total bilirubin (TBIL) [17.3(12.2, 28.2) μmol/L vs. 14.5 (9.4, 21.1) μmol/L, Z=2.25, P=0.024], direct bilirubin (DBIL)[5. 5 (3.4, 12.4) μmol/L vs. 4.4(2.9, 7.1) μmol/L, Z=2.00, P=0.045], and glutamyl aminotransferase (GGT)[193.0(64.3, 454.8)U/L vs. 105.5(53.5, 179.5)U/L, Z=2.02, P=0.043], alkaline phosphatase(ALP)[183(86, 351)U/L vs. 135(85, 188) U/L, Z=1.98, P=0.048] in PBC patients with dyslipidemia were significantly higher than thosein patients with normal serum lipids.Pearson regression analysis showed that in PBC patients with dyslipidemia, the ALT was positively corrected with TG and TC(r=0.248 and 0.272, P=0.015 and 0.008); ALB was positively correlated with LDL-C(r=0.335, P=0.002); DBIL was positively corrected with HDL-C(r=0.252, P=0.022); TC was positively correlated with ALP and GGT(r=0.313 and 0.346, P=0.002 and 0.001); GGT was positively correlated with LDL-C(r=0.251, P=0.022). Conslusion Increased TC and LDL-C were more common in PBC patients. PBC patients with dyslipidemia have more severe liver damage than the patients with normal serum lipids.

Objective : To measure and compare condyle-related indexes(volume, surface area, anterior space, upper space and posterior space) in adult female patients with different sagittal malocclusions with the aim of providing a reference for clinical treatment. Methods : The CBCT database of Qingdao Stomatology Hospital was searched to identify patients with high-angle adult skeletal malformations with the following classifications: classⅠ(n=30), class Ⅱ(n=30), and class Ⅲ(n=30). The CBCT images associated with the sample population were stored according to DICOM3.0 medical digital image communication standards. Mimics10.01 software was used to read and prepare three-dimensional reconstructions of the condylar, and the above-listed indicators were measured and statistically analyzed. Results : There were no significant differences between the right and left sides among the three groups (P > 0.05). For parameters including condylar anterior joint space and post-joint space, the differences among the three groups were significant (P < 0.05). There was no significant difference in parameters related to condylar articular space between classⅠand class Ⅱ(P > 0.05). The differences between skeletal classesⅠand Ⅲ and between skeletal ClassesⅡ, and Ⅲ were statistically significant (P < 0.05). Conclusion Condylar position varies among high-angle adult woman with skeletal malocclusions with different sagittal skeletal patterns.

Objective To investigate the characteristics of intestinal flora in infants with different feeding patterns.Methods Sixty-two cases of health infants(30-120 d)were divided into 4 groups according to their feeding patterns:breast feeding,imported powder milk feeding,domestic powder milk feeding and mixed feeding.Samples of their fresh feces in each group were collected and divided into sections equally:the bifidobacteria were isolated in anaerobic box and the number was counted for one section;for the other section,total DNA of intestinal flora was extracted and enterobacterial repetitive intergenic consensus (ERIC) fingerprints were amplified with the method of ERIC-PCR.After that,the specific bands observed in different groups were cloned and sequenced and alignmented.Results The colonies of bifidobacteria were more in breast feeding and mixed feeding groups[(9.10 ± 1.33) cfu/g;(8.62 ± 1.35) cfu/g]than those in domestic powder milk feeding and imported powder milk feeding groups[(7.62 ± 1.22) cfu/g;(7.32 ± 0.80) cfu/g,t =3.23,P ＜ 0.05];while there was no significant difference between breast feeding and mixed feeding groups,and between 2 powder milk feeding groups.Two specific bands were found from the ERIC fingerprints (A:1 100 bp mainly in breast feeding,domestic powder milk feeding and mixed feeding groups;B:1 000 bp mainly in imported powder milk feeding group).Sequencing and analysis of Basic Local Alignment Search Tool showed that homologous bacteria of A and B fragments were bifidobacterium longum.The encoding protein of A fragments might be related to the enzymes of carbohydrate metabolism,and B fragments were related to the enzymes of protein metabolism.Conclusions The colonies of bifidobacteria in intestinal tract are more in breast feeding and mixed feeding infants than those in formula feeding groups.The distribution of intestinal flora in domestic powder milk feeding infants is more similar to that of the breast feeding infants.

Objective To explore the effectiveness and safety of limited endoscopic sphincterotomy plus endoscopic papillary balloon dilation (ESBD)for patients with large common duct stones and periampul-lary diverticula (PAD).Methods Data of 40 patients with large common duct stones (diameter ≥10 mm) and PAD who underwent ESBD were retrospectively reviewed.The clinical feature,operation method,suc-cess rates of stone removal and early complications rates during hospitalization were evaluated according to PAD subtypes.Results The stone removal rate in first session was 90.0%(36 /40,with a median time of 29 minutes per procedure.Three patients underwent a second procedure to remove residual stones.The over-all stone removal rate was 97.5% (39 /40).The early complications rate was 15%(6 /40),including mild pancreatitis in two cases(5%),hyperamylasemia in two (5%),postoperative late bleeding in two (5%), which were cured with conservative treatment.No perforation,massive hemorrhage or death occurred.No significant differences in success stone removal rate and early complication rate were found between PAD sub-types.Conclusion ESBD is an effective and safe procedure for removing choledocholithiasis in patients with PAD,regardless of PAD subtypes.