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.

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.

Enhancing sensitivity of microbial fuel cell sensors for low concentration biodegradable organic matter detection: Regulation of substrate concentration, anode area and external resistance.

The relatively low sensitivity is an important reason for restricting the microbial fuel cell (MFC) sensors' application in low concentration biodegradable organic matter (BOM) detection. The startup parameters, including substrate concentration, anode area and external resistance, were regulated to enhance the sensitivity of MFC sensors. The results demonstrated that both the substrate concentration and anode area were positively correlated with the sensitivity of MFC sensors, and an external resistance of 210 Ω was found to be optimal in terms of sensitivity of MFC sensors. Optimized MFC sensors had lower detection limit (1 mg/L) and higher sensitivity (Slope value of the linear regression curve was 1.02), which effectively overcome the limitation of low concentration BOM detection. The essential reason is that optimized MFC sensors had higher coulombic efficiency, which was beneficial to improve the sensitivity of MFC sensors. The main impact of the substrate concentration and anode area was to regulate the proportion between electrogens and nonelectrogens, biomass and living cells of the anode biofilm. The external resistance mainly affected the morphology structure and the proportion of living cells of the anode. This study demonstrated an effective way to improve the sensitivity of MFC sensors for low concentration BOM detection.

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.

Feasibility of Shape-Memory Ni/Ti Alloy Wire Containing Tube Elevators for Transcrestal Detaching Maxillary Sinus Mucosa: Ex Vivo Study.

BACKGROUND: Osteotome sinus floor elevation is a less invasive approach to augment an insufficient alveolar bone at the posterior maxilla for dental implantation. However, this approach has some limitations due to the lack of sinus lift tools available for clinical use and the small transcrestal access to the maxillary sinus floor. We recently invented shape-memory Ni/Ti alloy wire containing tube elevators for transcrestal detaching maxillary sinus mucosa, and developed goat ex vivo models for direct visualizing the effectiveness of detaching sinus mucosa in real time during transcrestal maxillary sinus floor elevation. METHODS: We evaluated our invented elevators, namely elevator 012 and elevator 014, for their effectiveness for transcrestal detaching maxillary sinus mucosa using the goat ex vivo models. We measured the length of sinus mucosa detached in mesial and distal directions or buccal and palatal directions, and the space volume created by detaching maxillary sinus mucosa in mesial, distal, buccal and palatal directions using the invented elevators. RESULTS: Elevator 012 had a shape-memory Ni/Ti alloy wire with a diameter of 0.012 inch, while elevator 014 had its shape-memory Ni/Ti alloy wire with a diameter of 0.014 inch. Elevator 012 could detach the goat maxillary sinus mucosa in the mesial or distal direction for 12.1±4.3 mm, while in the buccal or palatal direction for 12.5±6.7 mm. The elevator 014 could detach the goat maxillary sinus mucosa for 23.0±4.9 mm in the mesial or distal direction, and for 19.0±8.1 mm in the buccal or palatal direction. An average space volume of 1.7936±0.2079 ml was created after detaching the goat maxillay sinus mucosa in both mesial/distal direction and buccal/palatal direction using elevator 012; while the average space volume created using elevator 014 was 1.8764±0.2366 ml. CONCLUSION: Both two newly invented tube elevators could effectively detach the maxillary sinus mucosa on the goat ex vivo sinus models. Moreover, elevator 014 has advantages over the elevator 012 for the capability to detach sinus mucosa.

The Future of IBD Therapy: Where Are We and Where Should We Go Next?

BACKGROUND: The advent of biologic agents opens up a new era for the treatment of inflammatory bowel disease (IBD). In this era, the treatment goal has evolved from the traditional goal of clinical remission to a combination of clinical remission, laboratory normalization and mucosal healing, designated as 'complete deep remission'. Such complete deep remission comprises a more ambitious disease control strategy that is believed to probably modify the natural course of IBD. KEY MESSAGES: To achieve this goal, optimization of current strategy and introduction of novel therapies have gained significant interest. In this concise review, we aim to provide an overview of the current status and future direction of IBD treatment. Specifically, we will describe the application of personalized therapy, development of new biologics, intestinal microbiome manipulation and out-of-the-box agents for IBD. CONCLUSIONS: More evidence is still desirable to better optimize the current treatment and apply novel biologics. Personalized medicine has the potential to optimize efficacy, decrease the risk of adverse events and minimize costs and should be proposed as a standard of care for the management of IBD.

[Analgesic effect of fentanyl in neonates during mechanical ventilation].

OBJECTIVE: To study the analgesic effect and safety of fentanyl in neonates receiving mechanical ventilation. METHODS: Thirty neonates receiving mechanical ventilation between December 2010 and February 2011 were randomized into drug intervention group and control group (n=15 each). In addition to the conventional treatment for both groups, the drug intervention group received fentanyl as the analgesic treatment. Heart rate, respiratory rate, blood pressure changes, and premature infant pain profile (PIPP) score before treatment and at 30 minutes, 2 hours, and 4 hours after treatment were recorded in both groups. Follow-up visits were performed for these infants after discharge, and the CDCC intellectual development scale for infants was applied to measure mental development index (MDI) and psychomotor development index (PDI) at 3, 6, 9, and 12 months of age. RESULTS: The respiratory rate and heart rate decreased in the drug intervention group after fentanyl treatment compared with the control group (P<0.05), and the PIPP scores in the drug intervention group was significantly lower than in the control group (P<0.05). The results of follow-up visits showed no significant differences in MDI and PDI at 3, 6, 9 and 12 months of age between the drug intervention and control groups (P>0.05). CONCLUSIONS: Fentanyl can relieve the pain response in neonates receiving mechanical ventilation, with no long-term adverse effects on neurodevelopment.

Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are becoming more common in Asia, but epidemiologic data are lacking. The Asia-Pacific Crohn's and Colitis Epidemiology Study aimed to determine the incidence and phenotype of IBD in 8 countries across Asia and in Australia. METHODS: We performed a prospective, population-based study of IBD incidence in predefined catchment areas, collecting data for 1 year, starting on April 1, 2011. New cases were ascertained from multiple overlapping sources and entered into a Web-based database. Cases were confirmed using standard criteria. Local endoscopy, pathology, and pharmacy records were searched to ensure completeness of case capture. RESULTS: We identified 419 new cases of IBD (232 of ulcerative colitis [UC], 166 of Crohn's disease [CD], and 21 IBD-undetermined). The crude annual overall incidence values per 100,000 individuals were 1.37 for IBD in Asia (95% confidence interval: 1.25-1.51; 0.76 for UC, 0.54 for CD, and 0.07 for IBD-undetermined) and 23.67 in Australia (95% confidence interval: 18.46-29.85; 7.33 for UC, 14.00 for CD, and 2.33 for IBD-undetermined). China had the highest incidence of IBD in Asia (3.44 per 100,000 individuals). The ratios of UC to CD were 2.0 in Asia and 0.5 in Australia. Median time from symptom onset to diagnosis was 5.5 months (interquartile range, 1.4-15 months). Complicated CD (stricturing, penetrating, or perianal disease) was more common in Asia than Australia (52% vs 24%; P = .001), and a family history of IBD was less common in Asia (3% vs 17%; P < .001). CONCLUSIONS: We performed a large-scale population-based study and found that although the incidence of IBD varies throughout Asia, it is still lower than in the West. IBD can be as severe or more severe in Asia than in the West. The emergence of IBD in Asia will result in the need for specific health care resources, and offers a unique opportunity to study etiologic factors in developing nations.

[The prevalence and characteristics of anemia in Crohn's disease in the Chinese].

OBJECTIVE: To investigate the prevalence and characteristics of anemia among patients with Crohn's disease (CD) in Chinese population and identify the possible risk factors. METHODS: A cross-sectional study was performed in 441 patients with CD enrolled from the First Affiliated Hospital of Sun Yat-Sen University between January 2003 and May 2012. The prevalence, severity, type of anemia in these patients was assessed when diagnosis was confirmed. A multivariate logistic regression including 122 patients was performed to screen risk factors of anemia. RESULT: The prevalence of anemia was 64.4% (284/441) with 69.0% (196/284) mild anemia, 28.9% (82/284) moderate anemia and 2.1% (6/284) severe anemia. The most common morphological classification was hypochromic microcytic anemia (43.7%, 124/284). Multivariate logistic regression showed the predictive factors for anemia were higher levels of modified Crohn's disease activity index (CDAI) (OR = 1.007, 95% CI 1.002-1.013), platelet count (OR = 1.007, 95% CI 1.001-1.012), erythrocyte sedimentation rate (OR = 1.024, 95% CI 1.000-1.048), penetrating behavior (OR = 16.952, 95% CI 2.626-108.626), structuring behavior (OR = 6.717, 95% CI 1.583-28.507), older age at diagnosis (OR = 1.065, 95% CI 1.012-1.121),and lower body mass index (BMI) (OR = 0.769, 95% CI 0.633-0.935). CONCLUSIONS: Anemia is a common complication in patients with CD among Chinese population. Activity of the underlying disease, older age at diagnosis, penetrating or structuring disease behavior and low BMI are the risk factors.

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.

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.

Risk factors for surgery and postoperative recurrence: analysis of a south China cohort with Crohn's disease.

BACKGROUND AND AIMS: To investigate the risk factors for primary surgery and postoperative recurrence in a cohort of Chinese Crohn's disease (CD) patients. METHODS: Medical notes of consecutive diagnosed patients from 2003 until 2010 were reviewed. Fifty-seven postoperative patients--finished regular follow-up--were recruited for postoperative recurrence analysis. RESULTS: One hundred eleven of 323 (34.4%) patients of this cohort underwent primary surgery. The cumulative frequency of resection was 16.6%, 35.4%, 53%, and 94.5% for 1, 5, 10, and 30 years, respectively, after onset of disease. Male (OR: 1.994; 95% CI: 1.291-3.078, p = 0.002), stricture (OR: 4.832; 95% CI: 3.064-7.621, p = 0.000), or penetrating (OR: 4.923; 95% CI: 3.060-7.919, p = 0.000) were associated with an increased risk for primary surgery, while early use of immunomodulators was (OR: 0.438; 95% CI: 0.218-0.880, p = 0.020) associated with a decreased risk. Fifty-seven (21.1%) patients were diagnosed as postoperative clinical recurrence and the cumulative recurrence rates were 6.1%, 17.1%, and 36.8% for 1, 2, and 3 years, respectively. Perianal disease was associated with an increased risk for clinical recurrence (OR: 5.606; 95% CI: 1.59-19.766, p = 0.007). CONCLUSIONS: The operation frequency is high in CD. Male, penetrating, and stricture diseases are associated with an increased risk for primary surgery while early use of immunomodulators is associated with a decreased risk. The postoperative recurrence rate is also high. Patients with perianal disease are at higher risk for clinical recurrence.

High-dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus hernia.

BACKGROUND AND AIM: The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control. METHODS: Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24-h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual-channel 24-h pH test at the end of 4-week therapy. If the 24-h esophageal pH was still abnormal at the end of 4-week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24-h pH test was repeated at the end of the therapy. RESULTS: Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non-responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without. CONCLUSIONS: The standard-dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the "double-dose" esomeprazole therapy is required.

[The clinical and endoscopic efficacy of step-up and top-down infliximab therapy in Crohn's disease].

OBJECTIVE: To compare the efficacy of step-up and top-down infliximab therapy on patients with Crohn's disease (CD). METHODS: A prospective and open-label study was performed by the First Affiliated Hospital of SUN Yat-sen University during September 2007 to December 2010. Active CD patients who were refractory to steroid/immunomodulator or who were steroid-dependent were enrolled into step-up group. Active CD patients who had no steroid or immunomodulator therapy before were enrolled into top-down group. All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0, 2 and 6, followed by maintenance dosing every 8 weeks beginning at week 14. The clinical and endoscopic follow up lasted 30 weeks. Clinical symptoms and mucosal healing status under endoscopy were evaluated by follow-up at week 10 and 30. RESULTS: Forty-one CD patients were enrolled, with 24 in step-up group and 17 in top-down group. There were significant differences in disease duration (P = 0.006), combination therapy (P < 0.001) and severity of disease (P = 0.011) in baseline between step-up and top-down groups. At week 10 and 30 during treatment, the clinical remission rates in step-up group were 45.8% (11/24) and 58.3% (14/24) respectively; the mucosal healing rates in step-up group were 33.3% (8/24) and 54.2% (13/24) respectively; the clinical remission rates in top-down group were 70.6% (12/17) and 82.4% (14/17) respectively; and the mucosal healing rates in top-down group were 35.3% (6/17) and 52.9% (9/17) respectively. No significant differences in clinical remission and mucosal healing rates at both week 10 and 30 were observed between the two groups. The prevalences of adverse events in step-up and top-down group were 41.7% (10/24) and 29.4% (5/17) respectively (P = 0.422). CONCLUSION: Both step-up and top-down infliximab therapy can induce remission in more than half of CD patients, while top-down therapy might be more beneficiary to symptom and endoscopic remission.

[Multi-centered stratified clinical studies for psychological and sleeping status in patients with chronic constipation in China].

OBJECTIVE: To survey the emotional and sleeping status of patients with chronic constipation (CC) and analyze the relationship between psychological status and constipated symptoms. METHODS: From January 2009 to April 2010, 5 centers and 25 stratified hospitals were selected as the representatives of different regions of mainland China. The CC questionnaires including constipated symptoms, emotional and sleeping status, previous treatments and self-reported impact of constipation on health status, etc. Questionnaires were completed by well-trained physicians or investigators during face-to-face interviews. CC was diagnosed in accordance with the Rome III criteria. RESULTS: A total of 909 valid questionnaires analyzed. There were 258 males and 651 females with a mean age of (49 ± 19) years. 41.5% (377 cases) reported "tense feelings" and 38.3% (348 cases) "felt downcast" over the past 3 months. The patients feeling tense and(or) downcast "frequently" and "most of time" were around 11.3% (103 cases) and 9.4% (85 cases). And 43.8% (398 cases) patients reported sleeping disorders over the past 3 months. Regional differences existed in the comorbidities of psychological and sleeping disorders in CC patients, especially in those from tertiary hospitals. And it was the highest in Beijing area for tense feelings and downcast. The sleeping disorders were the most common in the patients from secondary hospitals, of which 66.1% (37/56) and 65.0% (39/60) were from Wuhan and Xi'an respectively. They were higher than Beijing and Guangzhou (39.7% (23/58), 29.0% (9/31), all P = 0.001). The patients from rural primary clinics suffered more sleeping disorders than those from urban primary cares (P = 0.026). About 35.0% (318 cases) and 28.4% (258 cases) patients reported their constipation was related with emotional and sleeping disorders. The comorbidities of psychological and sleeping disorders were more common in severe constipated patients than mild and moderate counterparts and resulted in more hospital visits (both P = 0.000). CONCLUSIONS: The CC patients often have the comorbidities of psychological and sleeping disorders with regional differences. The patients from the hospitals at various levels may present different spectrums of comorbidities of psychological and sleeping disorders. And the severity of CC influences the moods, sleeps and hospital visits.

Construction of Branched DNA-based Nanostructures for Diagnosis, Therapeutics and Protein Engineering.

Branched DNA with multibranch-like anisotropic topology serves as a promising and powerful building block in constructing multifunctional-integrated nanomaterials in a programmable and controllable manner. Recently, a series of branched DNA-based functional nanomaterials were developed by elaborate molecular design. In this review, we focused on the construction of branched DNA-based nanostructures for biological and biomedical applications. First, the molecular design and synthesis method of branched DNA monomer were briefly described. Then, the construction strategies of branched DNA-based nanostructures were categorially discussed, including target-triggered polymerization, enzymatic extension and hybrid assembly. Finally, the biological and biomedical applications including diagnosis, therapeutics and protein engineering were summarized. We envision that the review will contribute to the further development of branched DNA-based nanomaterials with great application potential in the field of biomedicine, thus building a new bridge between material chemistry and biomedicine.

Dynamic assembly of DNA-ceria nanocomplex in living cells generates artificial peroxisome.

Intracellular accumulation of reactive oxygen species (ROS) leads to oxidative stress, which is closely associated with many diseases. Introducing artificial organelles to ROS-imbalanced cells is a promising solution, but this route requires nanoscale particles for efficient cell uptake and micro-scale particles for long-term cell retention, which meets a dilemma. Herein, we report a deoxyribonucleic acid (DNA)-ceria nanocomplex-based dynamic assembly system to realize the intracellular in-situ construction of artificial peroxisomes (AP). The DNA-ceria nanocomplex is synthesized from branched DNA with i-motif structure that responds to the acidic lysosomal environment, triggering transformation from the nanoscale into bulk-scale AP. The initial nanoscale of the nanocomplex facilitates cellular uptake, and the bulk-scale of AP supports cellular retention. AP exhibits enzyme-like catalysis activities, serving as ROS eliminator, scavenging ROS by decomposing H2O2 into O2 and H2O. In living cells, AP efficiently regulates intracellular ROS level and resists GSH consumption, preventing cells from redox dyshomeostasis. With the protection of AP, cytoskeleton integrity, mitochondrial membrane potential, calcium concentration and ATPase activity are maintained under oxidative stress, and thus the energy of cell migration is preserved. As a result, AP inhibits cell apoptosis, reducing cell mortality through ROS elimination.

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.

The efficacy and safety of thalidomide in the treatment of refractory Crohn's disease in adults: a double-center, double-blind, randomized-controlled trial.

Background: Thalidomide is applied in therapy for refractory Crohn's disease (CD) in adults, but systematic and rigorous clinical evidence is scant. The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults. Methods: A double-center, double-blind, placebo-controlled, randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China. In the double-blind trial, patients were randomly assigned to 100 mg of thalidomide or placebo daily for 8 weeks. The primary outcome was considered as the clinical remission rate calculated based on the Crohn's disease activity index at the eighth week following thalidomide or placebo treatment. In open label, non-response to placebo was additionally treated with 8 weeks of thalidomide; all responders were continuously treated with thalidomide until the 48th week. Results: Twenty-five patients were randomly assigned to each group. At the eighth week, the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group (68.0% [17/25] vs 16.0% [4/25]; relative risk, 4.2; 95% confidence interval, 1.8-10.9, P < 0.001). After a 48-week follow-up, the continuous treatment rate of thalidomide was 46.3% (19/41). Adverse events during the whole process were reported in 58.5% of patients, mainly involving drowsiness, rash, and peripheral neuropathy that were mild and tolerable. Conclusion: Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults. And it could be one of the treatment options for refractory CD.