Comparison and development of machine learning for thalidomide-induced peripheral neuropathy prediction of refractory Crohn's disease in Chinese population.

BACKGROUND: Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurrence. AIM: To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables. METHODS: A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model. The National Cancer Institute Common Toxicity Criteria Sensory Scale (version 4.0) was used to assess TiPN. With 18 clinical features and 150 genetic variables, five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), specificity, sensitivity (recall rate), precision, accuracy, and F1 score. RESULTS: The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248 [P = 0.0004, odds ratio (OR): 8.983, 95% confidence interval (CI): 2.497-30.90], dose (mg/d, P = 0.002), brain-derived neurotrophic factor (BDNF) rs2030324 (P = 0.001, OR: 3.164, 95%CI: 1.561-6.434), BDNF rs6265 (P = 0.001, OR: 3.150, 95%CI: 1.546-6.073) and BDNF rs11030104 (P = 0.001, OR: 3.091, 95%CI: 1.525-5.960). In the training set, gradient boosting decision tree (GBDT), extremely random trees (ET), random forest, logistic regression and extreme gradient boosting (XGBoost) obtained AUROC values > 0.90 and AUPRC > 0.87. Among these models, XGBoost and GBDT obtained the first two highest AUROC (0.90 and 1), AUPRC (0.98 and 1), accuracy (0.96 and 0.98), precision (0.90 and 0.95), F1 score (0.95 and 0.98), specificity (0.94 and 0.97), and sensitivity (1). In the validation set, XGBoost algorithm exhibited the best predictive performance with the highest specificity (0.857), accuracy (0.818), AUPRC (0.86) and AUROC (0.89). ET and GBDT obtained the highest sensitivity (1) and F1 score (0.8). Overall, compared with other state-of-the-art classifiers such as ET, GBDT and RF, XGBoost algorithm not only showed a more stable performance, but also yielded higher ROC-AUC and PRC-AUC scores, demonstrating its high accuracy in prediction of TiPN occurrence. CONCLUSION: The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables. With the ability to identify high-risk patients using single nucleotide polymorphisms, it offers a feasible option for improving thalidomide efficacy in CD patients.

Clinical characteristics and risk factors of ovarian reserve decreases in women with Crohn's disease: a case-control study.

BACKGROUND: Crohn's disease (CD), often occurring in women of child-bearing age, can decline the fertility rate. However, whether it reduces ovarian reserve has been rarely reported. This study aimed to evaluate the ovarian reserve in women with CD from the perspective of anti-Müllerian hormone (AMH), and explore the factors that can decrease ovarian reserve. METHODS: A case-control retrospective study was designed. We analyzed the AMH levels in a total of 135 CD women and 878 healthy controls. Through propensity score matching, the subjects were assigned in a ratio of 1:3 to CD group (n = 121) and control group (n = 324). Both groups shared similar basic characteristics, like age, body mass index and smoking status. Serum AMH levels were measured by chemiluminescence. RESULTS: The AMH level in the CD group was significantly lower than that in the control group (2.17 ± 2.23 µg/L vs 3.95 ± 2.01 µg/L, 95%CI [1.34-2.21], P < 0.001). In both groups, the AMH levels decreased as age increased, but without between-group difference in the decreasing rate (P = 0.639). Multivariate analysis showed that age > 30 years (OR, 2.905; 95%CI [1.053-8.531], P = 0.017), disease activity (OR,4.314; 95%CI [1.561-12.910], P = 0.002) and thalidomide use (OR,12.628; 95%CI [4.351 -42.820], P < 0.001) were independent risk factors associated with decreased ovarian reserve (AMH<1.1µg/L). CONCLUSION: Ovarian reserve is lower in CD women than in healthy women. Age, CD activity and medication of thalidomide are risk factors that can aggravate the decline of ovarian reserve.

N6-Methyladenosine-Related lncRNAs Are Novel Prognostic Markers and Predict the Immune Landscape in Acute Myeloid Leukemia.

Background: Acute myelocytic leukemia (AML) is one of the hematopoietic cancers with an unfavorable prognosis. However, the prognostic value of N 6-methyladenosine-associated long non-coding RNAs (lncRNAs) in AML remains elusive. Materials and Methods: The transcriptomic data of m6A-related lncRNAs were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. AML samples were classified into various subgroups according to the expression of m6A-related lncRNAs. The differences in terms of biological function, tumor immune microenvironment, copy number variation (CNV), and drug sensitivity in AML between distinct subgroups were investigated. Moreover, an m6A-related lncRNA prognostic model was established to evaluate the prognosis of AML patients. Results: Nine prognosis-related m6A-associated lncRNAs were selected to construct a prognosis model. The accuracy of the model was further determined by the Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curve. Then, AML samples were classified into high- and low-risk groups according to the median value of risk scores. Gene set enrichment analysis (GSEA) demonstrated that samples with higher risks were featured with aberrant immune-related biological processes and signaling pathways. Notably, the high-risk group was significantly correlated with an increased ImmuneScore and StromalScore, and distinct immune cell infiltration. In addition, we discovered that the high-risk group harbored higher IC50 values of multiple chemotherapeutics and small-molecule anticancer drugs, especially TW.37 and MG.132. In addition, a nomogram was depicted to assess the overall survival (OS) of AML patients. The model based on the median value of risk scores revealed reliable accuracy in predicting the prognosis and survival status. Conclusion: The present research has originated a prognostic risk model for AML according to the expression of prognostic m6A-related lncRNAs. Notably, the signature might also serve as a novel biomarker that could guide clinical applications, for example, selecting AML patients who could benefit from immunotherapy.

miR-219a suppresses human trophoblast cell invasion and proliferation by targeting vascular endothelial growth factor receptor 2 (VEGFR2).

OBJECTIVE: Vascular endothelial growth factor (VEGF) plays a critical role in regulating trophoblast cell invasion and proliferation, involved in a variety of pregnancy complications, such as spontaneous abortion and pre-eclampsia. Numerous studies have revealed that microRNAs (miRNAs) are participated in a series of molecular processes that regulate cell function, such as cell invasion, proliferation, and apoptosis. Vascular endothelial growth factor receptor 2 (VEGFR2), a receptor of VEGF, has been shown to be involved in trophoblast function. However, the relation between miRNA and VEGFR2 and their role in trophoblast function remain to be elucidated. METHODS: The effect of miR-219a on the trophoblast function has been explored using luciferase reporter, transwell, qRT-PCR, western blot, bromodeoxyuridine (BrdU), ELISA, immunofluorescent staining, and tube formation assays. RESULTS: In the current study, we observed that through targeted inhibition of VEGFR2 expression by miR-219a, the function of VEGFR2 as well as the downstream PI3K/AKT/NF-κB signaling pathway were suppressed, leading to suppression of trophoblastic proliferation and invasion. Moreover, upregulation of VEGFR2 restored the miR-219a-inhibited cell proliferation, invasion, and tube formation. CONCLUSIONS: These results revealed that miR-219a played crucial roles in negatively regulating trophoblastic proliferation and invasion by suppression of the PI3K/AKT/NF-κB signaling pathway by targeting VEGFR2, therefore serving as a potential treatment method for the complications of pregnancy caused by trophoblastic dysregulation.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia.

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.

Layering-Triggered Delayering with Exfoliated High-Aspect Ratio Layered Silicate for Enhanced Gas Barrier, Mechanical Properties, and Degradability of Biodegradable Polymers.

Research on biodegradable polymers with the intention of fast, complete degradation in industrial compost (i-compost) for organic recyclability is paramount to identifying solutions to the problem of excessive plastic waste originating specifically from packaging. Conventional biodegradable polymers, such as polylactide (PLA), are far from optimum for this application due to the poor gas barrier properties and slow degradation. In the paper, a new concept (triggered degradation by delayering) is shown in which exfoliated, self-assembled sodium-hectorite (Hec) arranged in a layer-by-layer manner alternating with electrospun hot-pressed PLA provides strong gas barrier properties at high humidity and simultaneously accelerates the degradation of PLA, as tested in an enzymatic solution and i-compost. A thin composite film (thickness 56 µm) shows a tensile strength and modulus 58 and 2000 MPa, respectively, whereas oxygen permeability is as low as 0.0064 cm3 cm m-2 day-1 bar-1. Furthermore, the delayering of the composite film by swelling of Hec layer led to accelerated degradation of PLA, as shown in detail by enzymatic and compost degradation. Since such concepts for enhanced degradability are urgently needed for sustainable utilization of biodegradable polymers in plastic waste management, the present work is an important step ahead.

High-risk human papilloma virus infection and cervical neoplasm in female inflammatory bowel disease patients: a cross-sectional study.

BACKGROUND AND AIM: This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus (HPV) infection, especially types 16 and 18, and cervical neoplasia in female Inflammatory bowel disease (IBD) patients. METHODS: From July 2014 to January 2017, sexually active, female, Chinese IBD patients (21-60 years) and age-matched controls underwent cervical ThinPrep cytology testing (TCT) and high-risk HPV-DNA detection, and completed questionnaires about awareness of cervical cancer and HPV. Cervical dysplasia was categorized as cervical intraepithelial neoplasia (CIN) 1, 2 and 3. RESULTS: Of 124 IBD patients (30 ulcerative colitis and 94 Crohn's disease), 17 (13.7%) had high-risk HPV among whom 9 (7.3%) had HPV 16/18 infection and 4 (3.2%) had cervical CIN (3 CIN 3, 1 CIN 1) by pathology. Among 372 controls, 33 (8.9%) had high-risk HPV and only 1 (0.3%) had HPV 16 infection. Cervical TCT detected atypical squamous cells of unknown significance in one control; no control had CIN. The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls (both P < 0.001). The HPV-infection rate was higher in patients administered methotrexate [P = 0.005, odds ratio (95% confidence interval) 4.76 (1.471-15.402)] or more than two immunosuppressants [P = 0.013, odds ratio (95% confidence interval) 3.64 (1.255-10.562)]. Thiopurine, steroid, infliximab and disease behavior/location were not associated with HPV infection. Only 29.3% of patients had undergone cervical-cancer screening. Awareness of HPV infection and HPV-related cervical cancer was poor (28.2%). CONCLUSIONS: Female IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia, which may be associated with immunosuppressants. Education and routine follow-up with HPV-DNA testing and TCT are recommended, especially in female Chinese IBD patients.

Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn's disease patients.

BACKGROUND: Thiopurine-induced leukopenia (TIL) is a life-threatening toxicity and occurs with a high frequency in the Asian population. Although nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) variants significantly improve the predictive sensitivity of TIL, more than 50% of cases of this toxicity cannot be predicted by this mutation. The potential use of the 6-thioguanine nucleotide (6TGN) level to predict TIL has been explored, but no decisive conclusion has been reached. Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes? AIM: To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes. METHODS: Patients' clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017. NUDT15 R139C, thiopurine S-methyltransferase, and 6TGN concentrations were measured. RESULTS: A total of 411 Crohn's disease patients were included. TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8 × 108 red blood cells (RBC), which was not different from that of patients without TIL (P = 0.071). Then, we compared the 6TGN levels based on NUDT15 R139C. For CC (n = 342) and CT (n = 65) genotypes, the median 6TGN level in patients with TIL was significantly higher than that in patients without (474.8 vs 306.0 pmol/8 × 108 RBC, P = 9.4 × 10-5; 291.7 vs 217.6 pmol/8 × 108 RBC, P = 0.039, respectively). The four TT carriers developed TIL, with a median 6TGN concentration of 135.8 pmol/8 × 108 RBC. The 6TGN cut-off levels were 411.5 and 319.2 pmol/8 × 108 RBC for the CC and CT groups, respectively. CONCLUSION: The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes. Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.

Long Noncoding RNA HOTAIR Promotes Endometrial Carcinoma Cell Proliferation by Binding to PTEN via the Activating Phosphatidylinositol 3-Kinase/Akt Signaling Pathway.

Accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) exert essential biological functions in modulating the progression of endometrial carcinoma (EC). HOX transcript antisense intergenetic RNA (HOTAIR) has been widely recognized as a crucial mediator in various tumors, including EC. However, the specific molecular mechanism of HOTAIR in the development of EC remains to be further explored. In the present study, we demonstrated that HOTAIR was significantly upregulated in EC tissues; this was negatively correlated with PTEN but positively correlated with phosphatidylinositol 3-kinase (PI3K) and Akt. Overexpression of HOTAIR promoted proliferation and inhibited apoptosis of EC cells, similar to PTEN knockdown. Additionally, RNA pulldown demonstrated the direct binding relationship between HOTAIR and PTEN. Furthermore, HOTAIR activated the PI3K/Akt pathway to promote EC progression by suppressing PTEN in vivo Taking these results together, we revealed that high expression of HOTAIR promoted cell proliferation and inhibited apoptosis through activating the PI3K/Akt pathway via binding to PTEN, which might provide a prognostic marker and therapeutic target of EC.

Long non-coding RNA Linc00483 accelerated tumorigenesis of cervical cancer by regulating miR-508-3p/RGS17 axis.

OBJECTIVES: The aim of this study was to uncover the underlying mechanisms of cervical cancer progression and provide potential therapeutic targets for its treatment in clinic. MATERIALS AND METHODS: Real-Time qPCR was used to determine the expression levels of Linc00483, miR-508-3p and RGS17 mRNA in cervical cancer tissues and cell lines. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay was conducted to determine cell apoptosis. Western Blot was performed to detect protein expression levels. Wound healing and Transwell assay were employed to determine cell migration and invasion respectively. Online software (TargetScan, miRDB and miR TarBase) were used to predict the regulating mechanisms of Linc00483, miR-508-3p and RGS17, which were validated by dual-luciferase reporter gene system. In vivo tumor-bearing mice models were established to validate the cellular results. RESULTS: Linc00483 aberrantly overexpressed in both cervical cancer tissues and cell lines comparing to the Control groups. Knock-down of Linc00483 inhibited cervical cancer cell proliferation, invasion as well as migration, and promoted cell apoptosis. In addition, miR-508-3p was identified as the downstream target of Linc00483, and miR-508-3p inhibitor abrogated the inhibiting effects of downregulated Linc00483 on cervical cancer cell viability. Furthermore, the expression levels of Linc00483 was positively correlated with RGS17 in the clinical samples and overexpressed Linc00483 increased RGS17 expression levels in cervical cancer cells by sponging miR-508-3p. The in vivo experiments showed that knock-down of Linc00483 inhibited cervical cancer cell tumorigenesis and lung metastasis in mice models. CONCLUSIONS: Knock-down of Linc00483 inhibited the development of cervical cancer by regulating miR-508-3p/RGS17 axis.

Risk factors for colorectal neoplasia in patients with underlying inflammatory bowel disease: a multicenter study.

BACKGROUND: This study sought to evaluate the risk factors for the development of colitis-associated neoplasia (CAN) in Chinese patients with inflammatory bowel disease (IBD). METHODS: IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers. In addition to initial pathology evaluation, a CAN diagnosis was confirmed by two expert pathologists. Patients with CAN (n = 29) were compared with non-CAN controls (n = 87). Matching was performed for gender and IBD type with a ratio of three controls to one subject. RESULTS: Of the 29 patients with CAN, 8 (27.6%) had colorectal cancer (CRC), 20 (69.0%) had a final diagnosis of low-grade dysplasia and 1 (3.4%) had high-grade dysplasia. Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN, with odds ratios of 1.09 [95% confidence interval (CI): 1.04-1.14, P < 0.001] and 1.14 (95% CI: 1.03-1.27, P = 0.013), respectively. Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis (P = 0.012) and had longer IBD durations (P = 0.019). CONCLUSIONS: Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: Management.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Trachway video intubating stylet allows for optimization of electromyographic endotracheal tube placement for monitored thyroidectomy.

BACKGROUND: Endotracheal tube-based surface electrodes are now commonly applied to measure evoked electromyographic (EMG) response of the vocal cord during monitored thyroidectomy. The aim of the study was to determine the incidence of difficult intubation and to assess the effectiveness of using video-assisted intubating stylet (Trachway) for EMG tube placement in patients undergoing monitored thyroidectomy. METHODS: Medical records were collected from consecutive patients undergoing thyroid surgery before and after implementation of the protocol. A total of 748 patients intubated with EMG tube for monitored thyroidectomy by the same team were enrolled in this study. Patient allocation was based on intubation technique either conventional direct laryngoscopy (n=336) or Trachway (n=412). The intubation difficulty was assessed and analyzed. RESULTS: The overall incidence of difficult intubation was 4.4%. Incidence of difficult intubation was significantly lower in patients with the Trachway procedure (2.7%) than direct laryngoscopy (6.5%, P=0.01). The incidence of "unable to intubate" (>3 attempts, or change airway device or anesthesiologist) also significantly reduced from 2.3% to 0.5% after introduction of the Trachway intubating stylet (P=0.02). CONCLUSIONS: We conclude that the incidence of difficult intubation was significantly lower with Trachway than direct laryngoscopy. The Trachway video-intubating stylet is useful and helpful to reduce EMG tube intubation difficulty for monitored thyroidectomy.

Family history and disease outcomes in patients with Crohn's disease: A comparison between China and the United States.

AIM: To investigate the differences in family history of inflammatory bowel disease (IBD) and clinical outcomes among individuals with Crohn's disease (CD) residing in China and the United States. METHODS: We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States. We compared the prevalence of IBD family history and history of ileal involvement, CD-related surgeries and IBD medications in China and the United States, adjusting for potential confounders. RESULTS: We recruited 49 participants from China and 145 from the United States. The prevalence of family history of IBD was significantly lower in China compared with the United States (China: 4.1%, United States: 39.3%). The three most commonly affected types of relatives were cousin, sibling, and parent in the United States compared with child and sibling in China. Ileal involvement (China: 63.3%, United States: 63.5%) and surgery for CD (China: 51.0%, United States: 49.7%) were nearly equivalent in the two countries. CONCLUSION: The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States. Despite the potential difference in etiology, surgery and ileal involvement were similar in the two countries. Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.

Standard-dose versus low-dose azathioprine in the treatment of Crohn's disease: A prospective randomized study.

OBJECTIVE: Azathioprine (AZA) is widely used to treat Crohn's disease (CD) with a recommended dose of 2-2.5 mg/kg per day for Westerners. Asian patients are suggested to take a lower dose. However, many clinicians reported poor efficacy with a reduced dose. This study aimed to explore a efficient and safe dose of AZA providing the best efficacy for Chinese CD patients. METHODS: Fifty patients with active CD were enrolled and randomized into two groups (n = 25 each). All other treatments were the same except that group A received 1 mg/kg per day and group B took 2 mg/kg per day of AZA. Complete remission (CR) rate and response rate at weeks 12, 24 and 48 were assessed by using intent-to-treat (ITT) and per-protocol (PP) analyses. Adverse events and recurrence rate were also evaluated. RESULTS: At week 48, CR rate and response rate in group B (ITT: 50.0% and 59.1%; PP: 57.9% and 68.4%) were significantly higher than those in group A (ITT: 13.0% and 17.4%; PP: 16.7% and 22.2%) (P < 0.05). Nine adverse events occurred, including pancreatitis (n = 1), arthritis (n = 2) and myelosuppression (n = 6). There was no significant difference in adverse events between the two groups. However, recurrence rate was significantly higher in group A than in group B (P = 0.042). CONCLUSION: AZA 2 mg/kg per day is more appropriate than 1 mg/kg per day for Chinese CD patients with a high efficacy, a low recurrence rate and not increased adverse events.

Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer.

AIM: To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS: Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with Oligofectamine(TM) to knock down the MIF expression, with the NC group and mock group (Oligofectamine(TM) alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT-PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS: The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific siRNA compared with the control siRNA and mock groups (P < 0.001 for all). CONCLUSION: MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.