Risk of metastasis and survival in patients undergoing different treatment strategies with T1 colonic neuroendocrine tumors.

PURPOSE: The efficacy and safety of local excision (LE) for small (< 1‒2 cm) colonic neuroendocrine tumors (NETs) is controversial due to the higher metastasis risk when compared with rectal NETs. The study aimed to evaluate the metastasis risk of T1 colonic NETs and compare patients' long-term prognosis after LE or radical surgery (RS). METHODS: The Surveillance Epidemiology and End Results database was used to identify patients with T1 colonic NETs (2004‒2015). Multivariable logistic regression was performed to assess factors associated with metastasis risk. Propensity score matching was used to balance the variables. Cancer-specific survival (CSS) and overall survival (OS) were calculated to estimate the prognosis of patients with T1N0M0 colonic NETs who underwent LE or RS. RESULTS: Of the 610 patients with colonic NETs, 46 (7.54%) had metastasis at diagnosis. Tumor size (11-20 mm) (OR = 9.51; 95% confidence interval (CI): 4.32‒21.45; P < 0.001), right colon (OR = 15.79; 95% CI 7.20‒38.56; P < 0.001), submucosal infiltration (OR = 2.08; 95% CI 0.84‒5.57; P = 0.125) were independent risk factors associated with metastasis. Of the 515 patients with T1N0M0 colonic NETs, the overall long-term prognosis of LE was as good as that of RS groups (after matching, 5-year CSS: 97.9% vs. 94.6%, P = 0.450; 5-year OS: 92.7% vs. 85.6%, P = 0.009). CONCLUSION: Tumor size (11‒20 mm) and site (right colon) are associated with metastasis in T1 colonic NETs. In the absence of metastasis, LE could be a viable option for 0‒10 mm T1 colonic NETs with well/moderate differentiation in the left colon in terms of long-term survival.

[Application of modified fusion convergence index in intermittent exotropia].

Objective: To investigate a modified fusional convergence parameter-total convergence amplitude/distance angle and its relationship with exotropia control, stereoacuity, and other visual functions in intermittent exotropia. Methods: The cross-sectional study included children diagnosed with intermittent exotropia at the First Affiliated Hospital of Nanjing Medical University from August 2020 to June 2021. A modification was made by combining total convergence amplitude using synoptophore and distance angle at distance using prism bars to calculate total convergence amplitude/distance angle. Exotropia control at distance and near measured by Office-based Scale for Assessing Control was classified as good control (scale 0-1) and poor control (scale 2-5). Statistical analysis was performed using Spearman correlation analysis, Mann-Whitney U test, Fisher's exact test, χ2 test, logistic regression analysis, and mediation effect analysis. Results: The study included 212 patients, of which 105 (49.5%) were male and 107 (50.5%) were female. The median (interquartile range) age was 9.0 (8.0, 10.0) years. Of 211 cases, 201 (94.8%) had binocular fusional function, while 11 cases (5.2%) did not have binocular fusional function. Among patients with binocular fusional function, inverse correlation was observed between total convergence amplitude and exotropia control scores for both distance (r=-0.427, P<0.001) and near (r=-0.194, P=0.006). Total convergence amplitude/distance angle was an independent predictive factor for exotropia control at distance (OR=0.195; 95%CI, 0.060-0.630; P=0.006) and near (OR=0.252; 95%CI, 0.085-0.746; P=0.013). Stereoacuity at distance (OR=3.110; 95%CI, 1.311-7.379; P=0.010) and near (OR=2.780; 95%CI, 1.401-5.517; P=0.003) were also factors associated with distance exotropia control. Mediation analysis revealed that stereoacuity was not a mediating factor between the ratio and distance control (distance: P=0.066; near: P=0.181). In patients with ratio≥1.5 °/PD, all the 15 patients demonstrated good control. On the contrary, patients with ratio<1.5 °/PD showed worse exotropia control (distance: P=0.001; near: P=0.040) and larger angles of deviation (distance: P<0.001; near: P<0.001). Conclusion: The modified fusional ratio, total convergence amplitude/distance angle, combining synoptophore and prism bars, could be used to evaluate the severity of intermittent exotropia. A higher ratio may be associated with poorer exotropia control. Though it may also be associated with distance exotropia control, stereoacuity is not the mediating factor between the modified ratio and distance exotropia control.

Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography.

Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.

[Expression level of Wilms' tumor 1 gene and its correlation with clinical features in patients with myeloproliferative neoplasms].

Objective: To investigate the expression level of WT1 gene in patients with classical Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) and its correlation with clinical features. Methods: A retrospective study included 252 patients with newly diagnosed MPN in Zhongnan Hospital of Wuhan University from January 2015 to March 2023, including 128 males and 124 females, aged［M（Q1，Q3）］62 (53, 69) years. The WT1-positive group (n=93) and the WT1-negative group (n=159) were split based on the level of WT1 gene expression, and the variations in clinical indicators between the two groups were compared. Its levels of expression in each subtype and its relationships to thrombotic events and clinically significant variables were analyzed. As of March 31, 2023, the follow-up period [M (Q1, Q3)] was 12.0(6.5,21.0)months. The risk factors of thrombosis in MPN patients were analyzed by using the logistic regression analysis. Results: The WT1 gene expression level in the overall bone marrow samples of 252 patients with newly diagnosed MPN was 0.30% (0.10%, 1.10%). The expression level in primary myelofibrosis (PMF) patients was 1.45% (0.41%, 3.24%), which was higher than 0.15% (0.02%, 0.32%), 0.37% (0.16%, 1.09%) in essential thrombocythemia (ET) and polycythemia vera (PV) patients (both P<0.05). Positive correlations were found between WT1 gene expression levels and JAK2V617F gene mutation load, RDW, MPV (r=0.478, 0.346, 0.236, all P<0.01). While negative correlations between WT1 gene expression levels and PLT, LYM, PTTA, LDH were found (r=-0.339, -0.170, -0.206, -0.388, all P<0.01). Patients in the WT1-positive group exhibited a higher percentage of somatic symptoms, splenomegaly, positive JAK2V617F gene mutation, and higher levels of RDW, LDH, NEUT, and MPV compared to the WT1-negative group. In contrast, the proportion of triple-negative (negative for all three hot mutations of JAK2V617F, CALR and MPL) was lower, and the levels of PLT, LYM and PTTA were lower (all P<0.05). The thrombotic event rates of WT1-positive group and WT1-negative group were 32.3% (30/93) and 32.1% (51/159), respectively, and the difference was not statistically significant (P=0.883). Logistic regression analysis showed that male (OR=2.41,95%CI:1.02-5.71,P=0.046) and positive JAK2V617F gene mutation (OR=3.96,95%CI:1.50-10.42,P=0.005) were risk factors for thrombotic events in ET patients. Conclusions: WT1 gene expression is elevated in PMF patients and correlated with indicators of disease progression and transformation in MPN patients. It can be utilized as an auxiliary diagnostic indicator for classical MPN staging but is not correlated with the incidence of thrombotic events. Male and positive JAK2V617F gene mutation are risk factors for thrombotic events in ET patients.

[Comparative study of hypersensitive quantitative fecal immunochemical test and qualitative fecal occult blood test for colorectal cancer and advanced adenoma].

Objective: To evaluate the screening performance of hypersensitive quantitative fecal immunochemical test (hs-qFIT) and qualitative fecal occult blood test (FOBT) for colorectal cancer and advanced adenoma. Methods: Consecutive participants scheduled to undergo colonoscopy from April 2020 to April 2021 in Qilu Hospital of Shandong University were included in the study. All the participants were 50-75 years old and at moderate to high risk for colorectal cancer. Participants completed hs-qFIT and two kinds of qualitative FOBTs (colloidal gold method and chemical-immunization method) before colonoscopy. The sensitivities and specificities of hs-qFIT and two qualitative FOBTs for colorectal cancer and advanced adenoma were compared. Results: A total of 910 participants were enrolled in the study, including 451 males and 459 females, aged (59.6±6.4) years. There were 22 cases (2.4%) of colorectal cancer, 61 cases (6.7%) of advanced adenoma, 276 cases (30.3%) of non-advanced adenoma, 194 cases (21.3%) of non-adenomatous polyp, 85 cases (9.3%) of other colorectal lesion and 272 cases (29.9%) of non-colorectal lesion. The sensitivities of hs-qFIT for detecting colorectal cancer increased from 72.7% (95%CI: 49.6%-88.4%) to 100% (95%CI: 81.5%-100%) with cut-off value decreasing from 200 ng/ml to 10 ng/ml, and the sensitivities of both colloidal gold method and chemical-immunization method were 63.6% (95%CI: 40.8%-82.0%) (P=0.008). The detection stability of hs-qFIT for colorectal cancer was higher than colloidal gold method (P=0.016) and chemical-immunization method (P=0.031). The sensitivity for detecting advanced adenoma of hs-qFIT at 10 ng/ml was 52.5% (95%CI: 39.4%-65.2%), which was significantly higher than that of colloidal gold method (13.1%, 95%CI: 6.2%-24.8%, P<0.001) and chemical-immunization method (6.6%, 95%CI: 2.1%-16.7%, P<0.001). Conclusions: The sensitivity and detection stability of hs-qFIT for detecting colorectal cancer was higher than qualitative FOBT. Moreover, the sensitivity for detecting advanced adenoma can be further improved using a lower cut-off value.

Evaluation of an accelerated 3D modulated flip-angle technique in refocused imaging with an extended echo-train sequence with compressed sensing for imaging of the knee: comparison with routine 2D MRI sequences.

AIM: To accelerate the acquisition of high-resolution magnetic resonance imaging (MRI) by using the three-dimensional (3D) matrix sequence with compressed sensing and to compare it with conventional two-dimensional (2D) proton-density (PD) and fast spin-echo (FSE) sequences. MATERIALS AND METHODS: 3D matrix, 2D FSE, and PD sequences were acquired from 68 participants using 3 T magnetic resonance imaging (MRI). Two radiologists scored image quality independently on a four-point scale. The structural similarity index (SSIM), and signal- (SNRs) and contrast-to-noise ratios (CNRs) of different anatomical structures of the knee were assessed and compared between sequences using Wilcoxon signed-rank tests and Cohen's kappa. RESULTS: The median acquisition time reduction was 44.5%. There was a substantial to perfect agreement for the rating between the 3D matrix FSE and 2D FSE or PD sequences when evaluating cartilage, subchondral bone, and ligaments (κ=0.783-872, p>0.05). The mean SSIM values between the 3D matrix FSE and 2D FSE, and between the 3D matrix PD and 2D PD sequences was 0.994 and 0.971, respectively, which are acceptable. No significant differences were found in SNR between the 3D matrix FSE and 2D FSE, and between the 3D matrix PD and 2D PD sequences, even though the SNR appeared to be higher on routine 2D sequences. The CNR of subchondral bone-meniscus, subchondral bone-joint fluid, and meniscus-joint fluid did not differentiate significantly between the 3D matrix sequence and routine 2D sequences. CONCLUSIONS: 3D matrix reduced the acquisition time in routine clinical knee MRI without the loss in image quality, SNR, and CNR.

[Recommendations for the medication of rheumatic diseases in periconceptional period].

Rheumatic diseases are a kind of chronic inflammatory diseases mainly involving joints and surrounding tissues. Most patients with rheumatic diseases need long-term treatment, which is difficult to be avoided during pregnancy. Treatment efficacy, as well as maternal and fetal safety should be taken into account in the medical decision. Based on the domestic and foreign guidelines, consensus, diagnosis and treatment experience, Chinese Rheumatology Association developed the standardization of medication use in patients with rheumatic diseases preparing and during pregnancy, aiming on the application and precautions of commonly used medicines for rheumatic diseases in preparing pregnancy, pregnancy and lactation.

[Investigation and analysis of reproductive health status of female street cleaners in a district].

Objective: To explore the reproductive health status of the female street cleaners in Chaoyang district of Beijing and its influencing factors. Methods: In July 2018, a total of 647 questionnaires were sent out to female road cleaning and sanitation workers in the whole district, 613 of which were valid, with an effective rate of 94.7%. Frequency or percentage (%) is used for statistical description of counting data, and mean standard deviation is used for measurement data. The influencing factors were analyzed by 2 test. Results: The average age of 613 female road sweepers in Chaoyang District of Beijing was 42.01 (SD=6.69) years old, including 535 married female workers (87.28%) , 356 middle school and below educated (58.08%) , 292 non Beijing registered (47.63%) , accounting for (/613) , (/613) female workers working hours >8 hours per day 110 (17.94%) , weekly rest <2 days 341 (55.63%) . 144 (23.49%) women workers did not have regular gynecological examination, 119 (19.41%) had reproductive tract infections, 177 (28.87%) had abnormal menstruation in recent 6 months. Drinking, sexual behavior outside marriage, night shift and job satisfaction were all the influencing factors (P<0.05) . The increasing age, working years, drinking, household registration in other places and the decreasing satisfaction of women workers＇ rights and interests protection were all the influencing factors (P<0.05) . Conclusion: The reproductive health status of female road sweepers in Chaoyang District of Beijing is not optimistic.

Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis.

Alzheimer's disease (AD) genetics implies a causal role for innate immune genes, TREM2 and CD33, products that oppose each other in the downstream Syk tyrosine kinase pathway, activating microglial phagocytosis of amyloid (Aß). We report effects of low (Curc-lo) and high (Curc-hi) doses of curcumin on neuroinflammation in APPsw transgenic mice. Results showed that Curc-lo decreased CD33 and increased TREM2 expression (predicted to decrease AD risk) and also increased TyroBP, which controls a neuroinflammatory gene network implicated in AD as well as phagocytosis markers CD68 and Arg1. Curc-lo coordinately restored tightly correlated relationships between these genes' expression levels, and decreased expression of genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL1ß). In contrast, very high dose curcumin did not show these effects, failed to clear amyloid plaques, and dysregulated gene expression relationships. Curc-lo stimulated microglial migration to and phagocytosis of amyloid plaques both in vivo and in ex vivo assays of sections of human AD brain and of mouse brain. Curcumin also reduced levels of miR-155, a micro-RNA reported to drive a neurodegenerative microglial phenotype. In conditions without amyloid (human microglial cells in vitro, aged wild-type mice), Curc-lo similarly decreased CD33 and increased TREM2. Like curcumin, anti-Aß antibody (also reported to engage the Syk pathway, increase CD68, and decrease amyloid burden in human and mouse brain) increased TREM2 in APPsw mice and decreased amyloid in human AD sections ex vivo. We conclude that curcumin is an immunomodulatory treatment capable of emulating anti-Aß vaccine in stimulating phagocytic clearance of amyloid by reducing CD33 and increasing TREM2 and TyroBP, while restoring neuroinflammatory networks implicated in neurodegenerative diseases.

Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR) Registry XI: gender impact on long-term outcomes.

OBJECTIVE: The objective of this paper is to assess the role of gender on survival rate and causes of death and organ damage in systemic lupus erythematosus (SLE) patients in China from 2009 to 2015. METHODS: We conducted a multicenter cohort study to analyze the differences in outcome data between male and female SLE patients. A group of 1494 SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were enrolled in the Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR) registry from April 2009 to February 2010. All enrolled patients were followed up at least once per year from 2009 to 2015. For patients who could not attend the outpatient clinic, follow-up was conducted by telephone interview. We collected demographic data, clinical manifestations and damage scores (System Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)). Survival rates were evaluated using the Kaplan-Meier method. RESULTS: This study included 1352 women and 142 men. The five-year survival rates were 92.0% for men and 97.6% for women. The survival rates of males were significant lower than for females ( p = 0.019). Male patients received methylprednisolone pulse therapy and cyclophosphamide significantly more than female patients ( p = 0.010). During follow-up, 12 male patients and 66 female patients died. The most common cause of death was infection (41.7%) for men and active SLE disease (27.3%) for women. At the end of the study, the major accumulated organ damages included renal (8.5%) and musculoskeletal (7.7%), and nervous system (5.6%) for men and renal (8.8%) and musculoskeletal (6.7%) for women. There were no significant differences in SDI scores between the two groups at baseline and at the end of the study. CONCLUSIONS: Male SLE patients had lower survival rates than female patients. Male patients received more methylprednisolone pulse and cyclophosphamide therapy. The most common causes of death were infection for male patients and active SLE disease for female patients. The major accumulated organ damages were renal, musculoskeletal, and nervous system both for male and female SLE patients in China.

[Advances in epigenetic markers of dermatomyositis/polymyositis].

Idiopathic inflammatory myopathy (IIM) is a rare group of autoimmune diseases, characterized by chronic muscle weakness, muscle fatigue and infiltration of single nuclear cells in skeletal muscle. Its subtypes include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myositis (IMNM), and the most common subtypes are DM and PM. PM is an autoimmune disease mainly manifested by muscle damage. When the skin is involved, it is called DM. The incidence of IIM was relatively low, which was 1.16-19 per million people/year, but the mortality was high and the prognosis was poor. The pathogenesis of IIM is still unclear. Previous studies suggest that both immune and non-immune mechanisms are involved in its pathogenesis, especially cellular and humoral immunity. In recent years, researchers have conducted a number of studies on the pathogenesis of IIM, especially in the study of DM/PM with the application of high-throughput biometrics. Epigenetics is a discipline that refers to the genetic phenomena of DNA methylation spectrum, chromatin structure state and gene expression spectrum transferred between cells without any changes in DNA sequence, including DNA methylation, chromatin modification and non-coding RNA changes. A large number of studies have shown that epigenetic modification plays an important role in many diseases, especially in cancer. Recent studies have also found a series of epigenetic markers related to the occurrence and development of DM/PM, mainly in the aspect of non-coding RNA changes, such as miR-10a, miR-206, etc. And there has also been some research on DNA methylation. However, no studies have been reported on whether chromatin modification is involved in the pathogenesis of DM/PM. The pathogenesis of DM/PM is complex and diverse. With the development of research, certain microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) may become biological markers for the early diagnosis of DM/PM. Therefore, this paper mainly expounds the research progress of the biomarkers of DM/PM from the aspect of epigenetics.

[Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms].

OBJECTIVE: To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. METHODS: Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1ß(MIP-1ß), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. RESULTS: Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1ß, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1ß and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1ß (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1ß TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. CONCLUSION: There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

[Predictive value of cervical length measured by transvaginal ultrasound during the second and the third trimester of pregnancy for preterm birth in twin pregnancies].

Objective: To investigate the predictive value of cervical length (CL) measured by transvaginal ultrasound for preterm birth <32 weeks, <34 weeks in twin pregnancies in the second and the third trimester of pregnancy. Methods: A total of 490 twin pregnant women with CL measured by transvaginal ultrasound during the second trimester of pregnancy (20-24 weeks) and the third trimester of pregnancy (28-32 weeks) delivered in Peking University Third Hospital, and Tongzhou Maternal and Child Health Hospital from January 2014 to December 2017 were collected, and 161 cases out of which were measured by CL during both the second trimester and the third trimester of pregnancy. Based on the measured gestational weeks, 427 cases were in the second trimester group and 224 cases in the third trimester group. The predictive value of CL for preterm birth was evaluated by calculating the optimal cut-off point with sensitivity and specificity. Logistic regression analysis was used to assess the relationship between CL and preterm birth after adjusting for confounding factors (age of pregnant women, chorionic status, mulipara, assisted reproductive pregnancy and pre-pregnancy body mass index). Results: (1) The median CL of pregnant women in the second trimester group and the third trimester group were 36 mm (33-40 mm) and 28 mm (18-33 mm) respectively. In the second trimester group, 151 cases (35.4%, 151/427) were preterm birth and 276 cases (64.6%, 276/427) were full-term birth; the median CL of preterm and full-term pregnant women were 34 mm (30-37 mm) and 37 mm (34-40 mm), respectively, with significant difference (P<0.01). In the third trimester group, 100 cases (44.6%, 100/224) were preterm birth and 124 cases (55.4%, 124/224) were full-term birth; the median CL of preterm and full-term pregnant women were 22 mm (15-30 mm) and 31 mm (23-34 mm), respectively, with significant difference (P<0.01). (2) Prediction of preterm birth <32 weeks and <34 weeks was performed with CL in the second trimester group. The area under the receiver-operating characteristics curve were 0.78 (95%CI: 0.70-0.86) and 0.71 (95%CI: 0.64-0.79), respectively. The optimal cut-off points were 36.5 mm and 33.5 mm, respectively. After adjusting for confounding factors, CL was inversely associated with preterm birth <32 weeks and <34 weeks of gestation. (3) Prediction of preterm birth <32 weeks and <34 weeks were performed with CL in the third trimester group. The area under the receiver-operating characteristics curve were 0.86 (0.75-0.96) and 0.75 (0.67-0.84), respectively. The optimal cut-off points were 17.5 mm and 18.5 mm, respectively. After adjusting for confounding factors, CL was inversely associated with preterm birth at <32 weeks and <34 weeks of gestation. Conclusions: CL measured by transvaginal ultrasound in the second and the third trimester is a good predictor for preterm birth of twin pregnancy. CL≤36.5 mm and ≤33.5 mm at 20-24 weeks of gestation could predict preterm birth <32 weeks and <34 weeks respectively. CL≤17.5 mm and ≤18.5 mm at 28-32 weeks of gestation could predict preterm birth <32 weeks and <34 weeks respectively.

Flotillin 1 is differentially expressed in human epithelial ovarian tumors.

Although Flotillin 1 (FLOT1) is highly expressed in various human cancers, its relationship with ovarian cancer (OC) remains unknown. This study determines FLOT1 expression in human ovarian tumors and examines its effect on OC   cell proliferation. FLOT1 protein expression was assessed in a tissue microarray by immunohistochemical staining. We found that 81.48% malignant and 50% borderline tumors were FLOT1 protein-positive, whereas benign tumors and normal ovarian tissues were negative. The staining was strongest in serous malignant tumor and transitional cell carcinoma and weakest in mucinous tumor. Differentially expressed FLOT1 in freshly isolated serous tumors was confirmed by Western blot and we then evaluated FLOT1 expression association with OC patients' clinical characteristics. Histological typing established that FLOT1 protein expression was significantly associated with serous tumor (P Keywords: cell proliferation, epithelial ovarian cancer, FLOT1, miRNA, therapeutic target, tumorigenesis.

[The clinical characteristics, diagnosis and treatment of patients with gout in China].

Objective: To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China. Methods: Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results: (1) The ratio of male to female in patients with gout was 14.7∶1. The mean age of onset was (48.8±15.1) years old. Mean serum urate level was (526.7±132.3) µmol/L. Patients' education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity [51.9%(3 536/6 814)]; (3) Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia. Most patients had the disease less than 5 years, and the longer the course, the more flares in the previous year of entry; (4) Febuxostat was the mostly used urate-lowering medication. 20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration, and 18.9%(267/1 412), 29.1%(215/739) and 38.1%(101/265) of them reached the control target of serum urate levels, respectively. After treatment, patients' liver function was not affected, but serum creatinine levels decreased significantly. Conclusions: The proportion of gout patients who reach target serum urate level is very low. Further steps including education and survey need to be carried on.

[Immunometabolism and systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease, characterized by production of pathogenic autoantibodies and wide involvement of multiple systems. Damageofimmune tolerance and imbalance of immune homeostasis lead to the production of autoantibodies and the injuries of multiple organs and systems. In recent years, plenty of studies have identified that immunometabolism affects survival status of certain cells, also cell activation, differentiation and effector functions. Conversely, immune cells with different functions or differentiational status upregulate specific metabolic pathways to maintain their identities. In response to outer stimulations, naive immune cells differentiate into activated cells, accompanied with a series of immunometabolism changes. Therefore, abnormal immunometabolism can induce global imbalance of immune homeostasis, which further results in the initiation and development of autoimmune diseases, including SLE. Multiple abnormalities of immunometabolism have been found in patients with SLE or mouse models of lupus. Immune cells involved in the development of SLE, such as T cells, B cells, dendritic cells and macrophages present various metabolic abnormalities and pathological phenotypes. Among these cells, CD4+ T cells play predominant roles in the pathogenesis of SLE. Lots of studies demonstrated that CD4+ T cells and their subsets were in abnormal immunometabolic status,which further resulted in the development of SLE. In CD4+ T cells from patients with SLE or mouse models of lupus, both levels of glycolysis and oxidative phosphorylation are significantly higher compared with healthy controls. However,mitochondrial abnormalities, decreased ATP production and increased level of oxidative stress also have been found in these cells, which play important roles in the production of reactive oxygen intermediates and autoantibodies. Aggregated lipids rafts and increased synthesis of glycosphingolipid and cholesterol also have been observed in the CD4+ T cells from patients with SLE, leading to the abnormally elevated TCR signaling. Moreover, mechanistic target of rapamycin (mTOR) signaling is activated in the CD4+ T cells from both patients with SLE or mouse models of lupus and participate in the metabolic abnormalities of pathological CD4+ T cells. Progressive understanding of immunometabolism give us new insights of the pathogenesis of SLE and provide us with more therapeutic targets in the treatment of SLE.

Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and subphenotypes in the Han Chinese population.

BACKGROUND: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population. OBJECTIVES: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS). METHODS: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells. RESULTS: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls. CONCLUSIONS: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.

Chinese SLE Treatment and Research group (CSTAR) registry VII: prevalence and clinical significance of serositis in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To investigate both the prevalence and clinical characteristics of serositis in Chinese patients with systemic lupus erythematosus (SLE) in a large cohort in the Chinese SLE Treatment and Research group (CSTAR) database. METHODS: A prospective cross-sectional study of patients with SLE was conducted based on the data from the CSTAR registry. Serositis was defined according to the 1999 revised American College of Rheumatology (ACR) criteria for SLE - that is, pleuritis/pleural effusion and/or pericarditis/pericardial effusion detected by echocardiography, chest X-ray or chest computerized tomography (CT) scan. Peritonitis/peritoneal effusion were confirmed by abdominal ultrasonography. We analysed the prevalence and clinical associations of serositis with demographic data, organ involvements, laboratory findings and SLE disease activity. RESULTS: Of 2104 patients with SLE, 345 were diagnosed with serositis. The prevalence of lupus nephritis (LN), interstitial lung disease and pulmonary arterial hypertension, as well as the presence of leukocytopenia, thrombocytopenia, hypocomplementemia and anti-dsDNA antibodies was significantly higher in patients with serositis (P < 0.05). Significantly higher SLE disease activity scores were found in patients with serositis compared to those patients without serositis (P < 0.05). Lupus-related peritonitis had similar clinical manifestations and laboratory profiles as serositis caused by SLE. CONCLUSIONS: There is a significant association of nephropathy, interstitial lung disease, pulmonary arterial hypertension, hypocomplementemia, leukocytopenia, thrombocytopenia and elevated anti-dsDNA antibodies with serositis. The results suggest that higher SLE disease activity contributes to serositis development, and should be treated aggressively.

A chemical-structural model for coherent martensite/parent interface in Mn-based antiferromagnetic shape memory alloys.

The martensite/parent coherent interface of Mn-based shape memory alloys (SMAs) is a significant part in the research of their martensitic transformation, reversible shape memory effect and magnetic shape memory effect. In the present work, a chemical-structural model was proposed to calculate the martensite/parent coherent interfacial energy of Mn-X (X = Cu, Fe) alloys. In this model, the coherent heterophase interfacial energy consists of chemical and structural parts. Resulting from the formation process of the heterophase interface, the chemical interfacial energy is expressed as the incremental value of bond energy, while the structural part is obtained by calculating the interfacial strain energy. The results show that the structural interfacial energy plays the chief role in the total interfacial energy, and the total interfacial energy decreases as the temperature rises when the alloy composition is fixed. In addition, the preferred orientation has noteworthy influence on the total interfacial energy. Using the proposed model, interfacial energy, interfacial entropy, interfacial enthalpy and interfacial heat capacity are found to be correlated with temperature and interface preferred orientation. Furthermore, the influences of alloy composition, modulus softening, and the index of the habit plane on the results were discussed.