The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

Objective In this study, we aimed to translate and revise the Summary of Diabetes Self-Care Activities( SDSCA) and the Confidence In Diabetes Self-care( CIDS) scales, to test the reliability and validity of the two scales in Chinese adult type 1 diabetes( T1D) patients. Methods In the first step, Chinese versions( C-SDSCA and C-CIDS) were developed conceptually equivalent to the English versions. And the investigation was conducted in 100 patients from Guangdong T1D Translational Medicine Study. 15 of them were randomly chosen to be retested 4 weeks later. Cronbach's α were used to assess reliability, and factor analysis to its validity. The relationship between scores of C-SDSCA and C-CIDS were analyzed using Spearman correlation analysis. Results The overall Cronbach's α of C-SDSCA was 0.72 and the retest reliability was 0.95( sub-scale:0.67-1.00) . 4 common factors were extracted by factor analysis, and the cumulative contribution was 87.39％. As for C-CIDS, the general Cronbach's α was 0.84 and the retest reliability was 0. 70 ( sub-scale: 0. 49-0. 86 ) . 6 common factors were extracted and the cumulative contribution was 75.41％. The score of the two scales was positively related(r=0.61, P<0.01). Conclusion The revised C-CIDS and C-SDSCA scales turn out to have good reliability and validity, and can be used as instruments to assess diabetes self-management efficacy and self-care activities of Chinese adult T1D patients.

Objective Chorioamnionitis in pregnancies with preterm premature rupture of membranes(PPROM) may lead to perinatal morbidity. There is no definite diagnostic method for detecting chorioamnionitis before delivery. In this retrospective study, the diagnostic value of five inflammatory markers, including white blood cell (WBC), neutrophil percentage (NEU), c-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) of subclinical chorioamnionitis in PPROM were investigated. Methods A total of 74 PPROM (Group A: 21 PPROM without infection; Group B: 43 PPROM with subclinical chorioamnionitis;Group C:10 PPROM with chorioamnionitis) and 46 controls (Group D:normal full-term pregnancies) were recruited from the Third Affiliated Hospital of Army Medical University between 2013 and 2017. The five markers were measured within 24 hours before the delivery. The diagnostic value of inflammatory markers for subclinical chorioamnionitis were assessed by t test and ROC curve. Results The levels of WBC, NEU and IL-6 in group A were significantly higher than those in group D (T=5.412, Z=-3.312, T=2.798, all P<0.05). The levels of five inflammatory markers in group B and C were all significantly increased compare with group D(Zb=-5.797, Zb=-5.296, Zb=-5.116, Zb=-3.279, Zb=-4.36, Tc=7.732, Zc=-4.622, Zc=-4.591, Zc=-3.509, Zc=-4.387,all P<0.05). Group B CRP, IL-6 and PCT levels were significantly higher than those of group A(Z=-3.10, Z=-2.95, Z=-2.202, all P<0.05). All five markers of group C were significantly higher than those of group A(T=-5.285, Z=-2.536, Z=-3.819, Z=-3.228, Z=-3.719, all P<0.05). The levels of WBC, NEU and IL-6 in group C were significantly higher than those in PPROM group B(Z=-3.296, T=-2.738, Z=-3.501, all P<0.05). In terms of predictive capability of subclinical chorioamnionitis, the individual area under ROC curve (AUC) of CRP, IL-6, and PCT were 0.740, 0.671, and 0.728 corresponding to the optimal cutoff 10.3 mg/L, 5.995 pg/ml, and 0.055 ng/ml respectively. The sensitivity value were 39.5％, 60.5％ and 74.4％, the specificity value were 100％, 85.7％and 61.9％.The area under the ROC curves of CRP+IL-6,CRP+PCT,IL-6+PCT and CRP+IL+6+PCT were 0.746, 0.805, 0.776 and 0.816. The sensitivity value were 51.2％, 74.4％, 81.4％ and 62.8％, the specificity value were 95.2％, 81％, 66.7％and 90.5％. Conclusions The model (combined with PCT, CRP and IL-6) may be helpful for the diagnosis of the subclinical chorioamnionitis in PPROM. Combined diagnosis of two markers in PCT,CRP and IL-6 could be superior to single inflammatory marker. Combined diagnosis of three could be better,which may provide a reference for clinical diagnosis.

Objective To summarize the clinical characteristics of children with Kawasaki disease (KD) in pediatric intensive care unit(PICU). Methods Medical record of children with KD at PICU were collected. At the same time,29 cases of KD in PICU were 1∶3 matched by age,gender and the time admitted in hospital with those admitted in general pediatric department(control group). Results PICU patients had longer length of hospital stay,longer fever duration compared with control group. In addition,patients in PICU had higher neutrophil percentage,C reaction protein,creatinine,urea nitrogen,N￣terminal natriuretic peptide and procalcitonin,but lower hemoglobin,blood platelet and albumin compared with the control group. What′s more,patients in PICU tended to find hemoglobin<100 g/L,platelet<150×109/L,albumin<30 g/L,abnor￣mal in urine routine and echocardiographic and more likely to have fever longer than 10 days when used intra￣venous immunoglobulin(IVIG) compared with control group. And PICU patients were more likely to require therapy with antibiotics,albumin,glucocorticoid and the second dose of IVIG. Some part of children in PICU group were treated with IVIG and glucocorticoid because of doubted severe infection before KD diagnosed,all patients in the control group used IVIG after the diagnosis. Conclusion Patients who admitted in PICU are severe and not typical in clinical manifestation. These patients are easily misdiagnosed as sepsis and more likely to be IVIG￣refractory and have coronary artery damage. We still worry that somebody might be misdi￣agnosed as sepsis,who are treated with IVIG and get better. Because they are not diagnosed as KD,these pa￣tient would not followe up like KD,but have potential risk of cardiovascular disease and need more alarming.

OBJECTIVE: To investigate the regulatory effect of metformin on regulatory T cells (Treg) in acidic environment. METHODS: CD4 CD25 Treg cells were obtained by magnetic bead sorting. Treg and conventional T cells (Tcon) cells were cultured for 24-72 h in pH 7.4 or pH 6.7 medium, and the cell proliferation, apoptosis and Foxp3 expression were detected by flow cytometry. Real-time PCR was used to detect the expression levels of the genes related with glucose metabolism. Thirty-two C57BL/6 male mouse models bearing subcutaneous prostate cancer xenograft derived from RM-1 cells were randomized into 4 equal groups for treatment with PBS, metformin, tumor vaccine, or both metformin and the vaccine. The treatment started on the 4th day following tumor cell injection, and metformin (100 mg/kg) or PBS was administered by intraperitoneal injection on a daily basis; the vaccine was intramuscularly injected every 4 days. The tumor size was continuously monitored, and the mice were euthanized on day 25 after tumor implantation to obtain tumor and blood samples. Flow cytometry was used to detect the changes in CD4, CD8, CD4Foxp3 cell subsets in the tumor tissue and peripheral blood. RESULTS: Treg cells showed significantly enhanced proliferation ( < 0.05) while the proliferation of Tcon cells was suppressed in acidic medium ( < 0.001). Treg cells cultured in acidic medium showed significantly increased expressions of OXPHOS-related genes pgc1a ( < 0.001) and cox5b ( < 0.01), which did not vary significantly in Tcon cells in acidic medium. Treg cells exhibited significantly decreased apoptosis in acidic medium ( < 0.01) with increased Foxp3 cells ( < 0.001) and intracellular alkaline levels ( < 0.01). Metformin obviously reversed the acid tolerance of Treg cells without producing significant effect on Tcon cells. In the animal experiment, both metformin ( < 0.05) and vaccine ( < 0.01) alone reduced the tumor volume, but their combined treatment more potently reduced the tumor volume ( < 0.001). Metformin alone did not obviously affect CD4 cells or CD8 cells but significantly decreased the percentage of CD4Foxp3 ( < 0.05); the vaccine alone significantly increased CD4 cells and CD8 cells ( < 0.001) and also the percentage of CD4Foxp3 cells ( < 0.05). The combined treatment, while reducing the percentage of CD4Foxp3cells to a level lower than that in the vaccine group ( < 0.01), produced the strongest effect to increase CD4 cells and CD8 cells ( < 0.01). CONCLUSIONS Metformin can inhibit the proliferation and function of regulatory T cells in an acidic environment and enhance the effect of tumor vaccine by reducing the proportion of Treg cells to achieve the anti-tumor effect.
Animals ; Cell Proliferation ; Forkhead Transcription Factors ; Male ; Metformin ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory

Objective: To analyze and explore the clinical characteristics and prognosis of patients with "double hit" multiple myeloma (MM) . Methods: We retrospectively analyzed 89 MM patients in our department of Shanghai Changzheng Hospital from 2010-2016. All patients were assayed by fluorescence in situ hybridization (FISH) and TP53 gene sequencing, based on Dr. Walker BA proposed the "double hit" MM concept, and then the clinical features and prognosis were evaluated. Results: In the results, 15 (16.85%) cases harbored "double hit" showed the median PFS of 8.4 months and the median OS 22.2 months, which was significantly lower than non-"double hit" patients with median PFS 14.2 months and the median OS 39.2 months, respectively (P<0.05) . Multivariate analysis displayed that the "double hit" was an independent poor prognostic factor on PFS (HR=2.171, 95%CI 1.206-3.907, P=0.010) and OS (HR=4.106, 95%CI 2.116-7.969, P<0.001) . Moreover, "double hit" MM patients had the higher adverse prognosis risk, which showed the shorter median OS and PFS than stage III of R-ISS patients (PFS 8.4 vs 11.8 months; OS 22.2 vs 24.3 months, P<0.05, respectively) . Conclusion Patients with "double hit" MM have a very poor clinical prognosis. Prospective clinical studies are urgently needed to improve these extra high risk patients.

Objective: To understand the characteristics relating to the etiology and complications of hand, foot and mouth disease (HFMD) based on data from the pilot National Sentinel Surveillance (NSS) program so as to explore the feasibility, advantages and disadvantages of the NSS. Methods: Data were extracted from the NSS system, conducted in 11 provinces of China from November 2015 to October 2016. Characteristics regarding the etiology, complications of HFMD and factors related to the positive rates of HFMD specimens were analyzed under the logistic regression method by SPSS 20.0 software. Results: A total of 4 783 specimens were collected, including 3 390 from mild, 1 390 from severe and 3 from death cases. The overall positive rate was 81.43% (3 895/4 783). Other enteroviruses (non EV71/Cox A16 enteroviruses) appeared the major serotype (52.68%, 1 482/2 813) for mild infection of the disease while EV71 was for the severe cases (65.31%, 706/1 081). The serotype spectrum revealed by the pilot NSS was almost identical with the existing surveillance system. Other enteroviruses tended to infect younger children (χ²=130.17, P<0.001) than EV71 and Cox A16, in China. The multivariate logistic regression results showed that higher positive rate was associated with specimens which were collected from males, at children’ hospitals, in peak seasons, timely and in stools. The positive rates presented downwarding trends with the extension of the onset-sampling interval (χ²=14.47, P<0.001 in stool specimen; χ²=31.99, P<0.001 in throat swab; χ²=24.26, P<0.001 in anal swab). Aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis appeared the top three complications of both EV71-associated and other enteroviruses-associated severe HFMD cases. Conclusions Factors as gender, season/place/timeliness of specimen collection, and types of hospital all appeared independently influenced the positive rates. NSS seemed feasible to be used as an alternative or supplement tool to the existing surveillance program in China.

Objective To observe the expressing changes of apolipoprotein M (ApoM),tumor necrosis factor-α(TNF-α) and monocyte chemoattractant protein-1 (MCP-1) in human retinal vascular endothelial cells (HRECs) under the high glucose culture condition and investigate the inhibitory effects of ApoM overepression on the expressions of TNF-α and MCP-1.Methods HRECs were cultured in DMEM containing 10％ fetal bovine serum and 5.5 mmol/L D-glucose and assigned to 6 groups.The cells in the normal control group were cultured in above culture medium;the cells in the high glucose group were treated using the DMEM with 30 mmol/L D-glucose;ApoM was transfected into the cells using lentiviral vector in the ApoM transfected group;lentiviral vector without ApoM sequence was transfected in the empty vector group;the cells transfected by empty vector were cultured in high glucose culture medium in the empty vector+high glucose group;the cells in the ApoM transfection+high glucose group were treated by ApoM sequence transfection and high glucose incubation.The relative expression of ApoM,TNF-α and MCP-1 mRNA was detected using real-time quantitative PCR,and the relative expression of ApoM protein was evaluated using Western blot assay.Results Compared with the normal control group,the mRNA expression levels of ApoM,TNF-α and MCP-1 in the high glucose group were significantly increased (t=5.517,3.295,2.555;all P＜0.05).HRECs grew well after infected with lentivirus.The relative expression level of ApoM mRNA in the ApoM transfected group was 236.400±39.270,which was significantly higher than 1.000±0.153 in the empty vector group (t=5.995,P＜0.01).An enhanced protein band of ApoM was seen in the ApoM transfected group,and the protein band was absent in the empty vector group.The relative expression band in the ApoM transfected group was 1.000± 0.249 and 2.978 ± 0.285 in the cells cultured with normal culture medium or high glucose culture medium,respectively,with a significant difference between them (t =5.056,P＜0.01).The relative expressions of TNF-α and MCP-1 in the mRNA levels were significantly different among the empty vector group,empty vector+high glucose group,ApoM transfected group and ApoM transfection + high glucose group (F =5.966,P =0.026;F =14.410,P =0.002).Compared with the empty vector+high glucose group,the relative expressions of TNF-α and MCP-1 mRNA were considerably reduced in the ApoM transfection+high glucose group (P=0.017,0.004).Conclusions High glucose environment up-regulates the expression of ApoM,MCP-1 and TNF-α in HRECs.Overexpression of ApoM inhibits the up-regulation of MCP-1 and TNF-α expression induced by high glucose.

Objective To investigate the effect and molecular mechanism of the combination of mechanical strain stimulation and icariin (ICA) on inhibiting the differentiation of osteoclasts induced by fatigue load stimulation. Methods The mouse mononuclear macrophage cell line RAW264.7 was cultured in vitro, and the blank control group was α-MEM complete medium. In the fatigue load group, RAW264.7 cells were treated with 5000 μεmechanical stretch strain, and then cultured in an osteoclast culture medium that was an α-MEM complete medium containing 40 ng/ml macrophage colony-stimulating factor and 40 ng/ml osteoclast differentiation factor. In the mechanical stimulation + ICA group, RAW264.7 cells were treated as the same procedure in the fatigue load group, and then cultured in an α-MEM complete medium containing 1 ×10 -5 mol/L ICA simultaneously with a 1000 μεtensile strain on the substrate. The activity of tartrate-resistant acid phosphatase (TRAP) was detected using a TRAP assay kit. The mRNA expression of the osteoclast marker genes, i.e. TRAP, cathepsin K(CTSK) and matrix metalloproteinase 9 (MMP-9) was detected by real-time RT-PCR. The nuclear translocation of nuclear factor kappa B (NF-κB) was analyzed by Western Blot. Results Compared with the fatigue load group, the combination of mechanical stimulation (1000 με substrate stretching) and ICA (1×10-5 mol/L) could significantly inhibit the activity of TRAP in osteoclasts (P<0.01) and reduce osteoclastosis. Moreover, that combination not only could down-regulate the mRNA expression of TRAP, CTSK and MMP-9 and the differences were statistically significant (all P<0.01), but also could inhibit the formation of osteoclasts by inhibiting the phosphorylation of P65, P50 and IκB-α in NF-κB signaling pathway. Conclusions The coupling of mechanical stimulation and ICA can effectively inhibit the osteoclast differentiation and the bone resorption induced by fatigue load, and the mechanism may involve regulating NF-κB signaling pathway.

Objective To observe whether ketamine improves the symptoms of post-traumatic stress disorder (PTSD).Methods Sixty male SD rats were randomized into four groups:groups CN,CK,PN and PK,15 in each.PTSD animal model was established by inescapable foot shock (IFS) procedure.In groups PK and CK,rats were treated with ketamine 2.5 mg/kg by intraperitoneal injection beginning at 30 min after the IFS procedure once a day for 14 days.Twelve rats were used for be havioral tests,and the others were sacrificed to collect hippocampus tissues for Western blot in each group 14 d after IFS procedure,respectively.The expression of neuroligin (NLGN)-1 was detected by Western blot.Results In the fear conditioning test,compared with group CN,the percent age of freezing time in total time in group PN was significantly increased (P＜0.01).Compared with group PN,the percent age of freezing time in PK group was significantly decreased (P＜0.01).In the water maze test,compared with group CN,the escape latency of group PN was significantly increased on day 2,3,4,5 of training period (P＜0.05).Compared with group PN,the escape latency of group PK was significantly decreased on day 2,4,5 of training period (P＜0.05).There was no significant difference in the time spent in the target quadrant.The expression of NLGN-1 in the hippocampus was significantly increased in PN group compared with group CN (P＜0.05);compared with group PN,the expression of NLGN-1 in the hippocampus was significantly decreased in PK group (P＜0.05).Conclusion The study suggest that the fear memory is significantly,increased and the hippo campus-dependent spatial learning capacity is impaired in the PTSD model rats.And the increased ex pression of hippocampal NLGN-1 may be involved in the development of PTSD.Ketamine mediated down regulation of NLGN-1 in the hippocampus might contribute to attenuating the fear memory and improving the hippocampus dependent spatial learning in the PTSD model rats.