Comparative efficacy and safety of anti-PD-1 therapies used in metastatic colorectal cancer: a systematic review and network meta-analysis

Objective: Systemic studies on anti-PD-1 therapy in patients with metastatic colorectal cancer (mCRC) with microsatellite instability or mismatch repair defects are lacking. We aimed to summarize the evidence regarding the efficacy and safety of pembrolizumab, nivolumab, ipilimumab, and tislelizumab in mCRC. Methods: Network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, eligible publications from PubMed, EMBASE, Web of Science, and Cochrane Library from 2016 to April 2023 were identified through a systematic literature review. Literature screening and data extraction were performed according to established criteria. The quality of the literature was evaluated using the Cochrane risk of bias tool, and statistical analysis was performed using Revman5.4 and R language. The main outcome indicators, DCR, ORR, PFS, and OS, were used to evaluate the effectiveness of the drugs, and the main outcome indicators AE and SAE were used to evaluate the safety of each program. Results: Fifteen studies with a sample size of 798 patients were included. In terms of effectiveness, the disease control rate DCR of PD-1 inhibitors was 0.727[95% CI:0.654-0.794]; objective response rate ORR was 0.448[95% CI:0.382-0.514]; and the 1-year progression-free survival rate was 0.551[95% CI:0.458-0.642]. The 1-year overall survival rate was 0.790[95% CI:0.705-0.865]. The adverse events associated with anti-PD-1 were 0.567[95% CI:0.344-0.778] in terms of safety. The total incidence of grade 3 or higher adverse events was 0.241[95% CI:0.174-0.313]. In the subgroup analysis results, the incidence of DCR in the nivolumab + ipilimumab group was 0.826[95% CI:0.780-0.869], the ORR was 0.512[95% CI:0.377-0.647], and the PFS was 0.668[95% CI:0.516-0.804]. The incidence of AE was 0.319 [95% CI:0.039-0.700] and SAE was 0.294 [95% CI:0.171-0.433]... (AU)

Cesarean section and the risk of allergic rhinitis in children: a systematic review and meta-analysis.

Multiple evidence indicates that perinatal factors make impact on immune development and affect offspring allergic rhinitis (AR) risk. In this systematic review and meta-analysis, we examined available published studies to clarify the relationship between cesarean section (C-section) and offspring AR in children. To explore the relationship between C-section, especially the special attention was paid to different cesarean delivery mode, and the risk of AR in children. Articles were searched using PubMed, Web of Science, EMBASE, Cochrane Library, China knowledge Network, Wanfang, and China Science and Technology Journal databases. A meta-analysis of 22 studies published before August 1, 2022, which included 1,464,868 participants, was conducted for statistical analysis with RevMan5.4. The correlation strength between C-section and offspring AR was determined by combining odds ratio (OR) and 95% confidence interval (95% CI). Meta-regression and subgroup analyses were used to explore potential sources of heterogeneity. Publication bias was detected using the funnel chart and Egger tests. Meta-analysis revealed that there was a significant correlation between C-section and children AR (OR = 1.19, 95% CI: 1.12-1.27, P < 0.001), especially C-section with a family history of allergy (OR = 1.82, 95% CI: 1.36-2.43, P < 0.001). Moreover, elective C-section (without genital tract microbe exposure) had the higher risk of offspring AR (OR = 1.24, 95% CI: 1.05-1.46, P = 0.010) compared with the whole study. Meta-regression demonstrated that sample size explained 38.0% of the variability between studies, and year of publication explained 18.8%. Delivery by C-section, particularly elective C-section and C-section with a family history of allergy can increase the risk of AR in children.

Gelatin nanofiber-reinforced decellularized amniotic membrane promotes axon regeneration and functional recovery in the surgical treatment of peripheral nerve injury.

Effective recovery of peripheral nerve injury (PNI) after surgical treatment relies on promoting axon regeneration and minimizing the fibrotic response. Decellularized amniotic membrane (dAM) has unique features as a natural matrix for promoting PNI repair due to its pro-regenerative extracellular matrix (ECM) structure and anti-inflammatory properties. However, the fragile nature and rapid degradation rate of dAM limit its widespread use in PNI surgery. Here we report an engineered composite membrane for PNI repair by combining dAM with gelatin (Gel) nanofiber membrane to construct a Gel nanofiber-dAM composite membrane (Gel-dAM) through interfacial bonding. The Gel-dAM showed enhanced mechanical properties and reduced degradation rate, while retaining maximal bioactivity and biocompatibility of dAM. These factors led to improved axon regeneration, reduced fibrotic response, and better functional recovery in PNI repair. As a fully natural materials-derived off-the-shelf matrix, Gel-dAM exhibits superior clinical translational potential for the surgical treatment of PNI.

Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence and Oxygen Self-Supply.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, its efficiency is hindered by three key parameters, namely, limited penetration depth of external light, tumor hypoxia, and self-aggregation of photosensitizers. Herein, we fabricated a novel "all-in-one" chemiluminescence-PDT nanosystem through the integration of an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) in hierarchically engineered mesoporous porphyrinic metal-organic framework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescence of Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and then absorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescence resonance energy transfer. The excited porphyrins then sensitize oxygen supplied by Hb to produce sufficient reactive oxygen species that kill cancer cells. The MOF-based nanocomposite demonstrates excellent anticancer activity both in vitro and in vivo, with eventually a 68.1% tumor inhibition rate after intravenous injections without external light irradiation. This self-illuminating, oxygen-self-supplying nanosystem integrates all essential components of PDT into one simple nanoplatform, demonstrating great potential for the selective phototherapy of deep-seated cancer.

Development and validation of a deep learning-based approach to predict the Mayo endoscopic score of ulcerative colitis.

Background: The ulcerative colitis (UC) Mayo endoscopy score is a useful tool for evaluating the severity of UC in patients in clinical practice. Objectives: We aimed to develop and validate a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. Design: A multicenter, diagnostic retrospective study. Methods: We collected 15120 colonoscopy images of 768 UC patients from two hospitals in China and developed a deep model based on a vision transformer named the UC-former. The performance of the UC-former was compared with that of six endoscopists on the internal test set. Furthermore, multicenter validation from three hospitals was also carried out to evaluate UC-former's generalization performance. Results: On the internal test set, the areas under the curve of Mayo 0, Mayo 1, Mayo 2, and Mayo 3 achieved by the UC-former were 0.998, 0.984, 0.973, and 0.990, respectively. The accuracy (ACC) achieved by the UC-former was 90.8%, which is higher than that achieved by the best senior endoscopist. For three multicenter external validations, the ACC was 82.4%, 85.0%, and 83.6%, respectively. Conclusions: The developed UC-former could achieve high ACC, fidelity, and stability to evaluate the severity of UC, which may provide potential application in clinical practice. Registration: This clinical trial was registered at the ClinicalTrials.gov (trial registration number: NCT05336773).

Why was this study done? The development of an auxiliary diagnostic tool can reduce the workload of endoscopists and achieve rapid assessment of ulcerative colitis (UC) severity. What did the researchers do? We developed and validated a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. What did the researchers find? The model that was developed in this study achieved high accuracy, fidelity, and stability, and demonstrated potential application in clinical practice. What do the findings mean? Deep learning could effectively assist endoscopists in evaluating the severity of UC in patients using endoscopic images.

Early exposure to infections increases the risk of allergic rhinitis-a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to provide evidence for early life care by meta-analyzing the relationship between infection during pregnancy and up to 2 years of age and the risk of subsequent allergic rhinitis (AR). METHODS: Published studies up to April 2022 were systematically searched in PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP. Literature screening, including quality assessment, was performed, and the effect values (OR, HR, RR) and 95% confidence intervals (95% CI) of infection during pregnancy and up to 2 years of age and allergic rhinitis were extracted from each qualified study. RESULTS: In total, 5 studies with a sample size of 82,256 reported the relationship between infection during pregnancy and offspring AR. Meta-analysis showed that maternal infection during pregnancy was associated with an increased risk of childhood AR in offspring (OR = 1.34, 95% CI: 1.08-1.67). Altogether, 13 studies with a sample size of 78,426 reported evidence of an association between infection within 2 years of age and subsequent AR in children. A pooled meta-analysis of all studies showed that early infection within 2 years of age was closely associated with childhood AR (OR = 1.25, 95% CI: 1.12-1.40), especially upper respiratory tract infection (OR = 1.32, 95% CI: 1.06-1.65) and gastrointestinal infections (OR = 1.37, 95% CI: 1.01-1.86), but ear infection showed similar results in the cohort study (OR = 1.13, 95% CI: 1.04-1.22). CONCLUSION: Current evidence suggests that infection during pregnancy, early upper respiratory infection, gastrointestinal infections and ear infection within 2 years of age would increase the risk of AR in children. Therefore, the prevention of infection during pregnancy and in infancy and young children needs to be emphasized.

Graphical education and appropriate time before elective colonoscopy make better bowel preparation.

Background: Inadequate bowel preparation leads to lower polyp detection rates, longer procedure times and lower cecal intubation rates. However, there is no consensus about high-quality bowel preparation, so our study evaluated graphical education and appropriate time before elective colonoscopy. Patients and Methods: We performed a secondary analysis of a national colorectal cancer screening programme of 738 patients. The patients were divided into a group given a graphical information manual (n = 242) or a word-only one (n = 496). They were also divided into groups according to the interval between bowel preparation and colonoscopy: 6-8 h (Group 1, n = 106), 9-12 h (Group 2, n = 228) and 13-17 h (Group 3, n = 402). All patients were scored according to the Boston Bowel Preparation Scale (BBPS) during the examination. Results: The bowel preparation of the graphical group was significantly better than the text group (P < 0.001). After adjustment, the bowel preparation score of Group 1 and Group 2 were both significantly higher than that of Group 3 (P = 0.012 and P = 0.032). Maximum BBPS was 6.31 when the interval time was 6.52 h (95% confidence interval: 5.95-6.66), and when the interval was <10 h, the BBPS was ≥6. Conclusion: High-quality bowel preparation was linked to graphical education and appropriate time before colonoscopy. We suggest that the interval between taking the first laxative and colonoscopy should be <10 h, preferably 6.5 h. Prospective multicentre research is needed to give more evidence of high-quality bowel preparation methods.

Prevalence and multilocus genotyping of Giardia duodenalis in Holstein cattle in Yunnan, China.

Giardia duodenalis is an important zoonotic protozoon, which can infect a variety of animals, causing diarrhea and even death of animals or humans. Dairy cattle have been implicated as important sources of human G. duodenalis. However, the information about the prevalence and genetic diversity of G. duodenalis in dairy cattle in China's Yunnan Province remains limited. This study investigated the occurrence and multilocus genotyping of G. duodenalis of Holstein cattle in Yunnan Province, China. A total of 524 fresh fecal samples of Holstein cattle were randomly collected from 8 farms in Yunnan. In this study, 27.5% (144/524) of tested samples were positive for G. duodenalis infection. The highest infection ratio was found in preweaned calves (33.7%), and the infection rates of postweaned calves, growing cattle, and adult cattle were 24.5%, 23.0%, and 17.3%, respectively. The sequence analysis of SSU rRNA gene showed that the predominant assemblage of G. duodenalis in this study was assemblage E (97.9%, 141/144), whereas assemblage A was identified only in three samples (2.1%, 3/144). All G. duodenalis-positive samples were further assayed with nested polymerase chain reaction (PCR) targeting ß-giardin (bg), triosephosphate isomerase (tpi), and glutamate dehydrogenase (gdh) genes, and 87, 41, and 81 sequences were obtained, respectively. Mixed infection of assemblages A and E of G. duodenalis was detected in three samples. Multilocus genotyping yielded 23 multilocus genotypes (MLGs). This is the first study that reveals the prevalence data of G. duodenalis in Holstein cattle in Yunnan Province, and the results of this study provided baseline data for the prevention and control of G. duodenalis infection in Holstein cattle in Yunnan Province, China.

Development and Validation of a Deep Neural Network for Accurate Identification of Endoscopic Images From Patients With Ulcerative Colitis and Crohn's Disease.

Background and Aim: The identification of ulcerative colitis (UC) and Crohn's disease (CD) is a key element interfering with therapeutic response, but it is often difficult for less experienced endoscopists to identify UC and CD. Therefore, we aimed to develop and validate a deep learning diagnostic system trained on a large number of colonoscopy images to distinguish UC and CD. Methods: This multicenter, diagnostic study was performed in 5 hospitals in China. Normal individuals and active patients with inflammatory bowel disease (IBD) were enrolled. A dataset of 1,772 participants with 49,154 colonoscopy images was obtained between January 2018 and November 2020. We developed a deep learning model based on a deep convolutional neural network (CNN) in the examination. To generalize the applicability of the deep learning model in clinical practice, we compared the deep model with 10 endoscopists and applied it in 3 hospitals across China. Results: The identification accuracy obtained by the deep model was superior to that of experienced endoscopists per patient (deep model vs. trainee endoscopist, 99.1% vs. 78.0%; deep model vs. competent endoscopist, 99.1% vs. 92.2%, P < 0.001) and per lesion (deep model vs. trainee endoscopist, 90.4% vs. 59.7%; deep model vs. competent endoscopist 90.4% vs. 69.9%, P < 0.001). In addition, the mean reading time was reduced by the deep model (deep model vs. endoscopists, 6.20 s vs. 2,425.00 s, P < 0.001). Conclusion: We developed a deep model to assist with the clinical diagnosis of IBD. This provides a diagnostic device for medical education and clinicians to improve the efficiency of diagnosis and treatment.

Self-Healing Alginate Hydrogel Formed by Dynamic Benzoxaborolate Chemistry Protects Retinal Pigment Epithelium Cells against Oxidative Damage.

Oxidative stress is considered as a major factor causing retinal pigment epithelium (RPE) dysfunction and finally leading to retinal diseases such as age-related macular degeneration (AMD). Developing hydrogels for RPE cell delivery, especially those with antioxidant feature, is emerging as a promising approach for AMD treatment. Herein, a readily prepared antioxidant alginate-based hydrogel was developed to serve as a cytoprotective agent for RPE cells against oxidative damage. Alg-BOB was synthesized via conjugation of benzoxaborole (BOB) to the polysaccharide backbone. Hydrogels were formed through self-crosslinking of Alg-BOB based on benzoxaborole-diol complexation. The resulting hydrogel showed porous micro-structure, pH dependent mechanical strength and excellent self-healing, remolding, and injectable properties. Moreover, the hydrogel exhibited excellent cytocompatibility and could efficiently scavenge reactive oxygen species (ROS) to achieve an enhanced viability of ARPE-19 cells under oxidative condition. Altogether, our study reveals that the antioxidant Alg-BOB hydrogel represents an eligible candidate for RPE delivery and AMD treatment.

Twelve-week peptide-based formula therapy may be effective in inducing remission of active Crohn disease among women who are pregnant or preparing for pregnancy.

BACKGROUND: Conventional treatment for Crohn disease (CD) in pregnancy includes mesalamine, thiopurine, and anti-tumor necrosis factor (TNF)-α agents. However, women may abstain because of complications, nonresponse, or potential adverse outcomes. Peptide-based formula therapy, through oral or nasogastric feeding without other food intake, is an effective and safe therapy for active CD. Herein, We confirmed the effectiveness and safety of peptide-based formula therapy for active CD in pregnant women or those preparing for pregnancy. METHOD: Outcomes of peptide-based formula therapy to induce CD remission during pregnancy preparation and the conception period were evaluated retrospectively among 14 women. Efficacy was evaluated as the change in serum indices and inflammatory markers after 12-week treatment. Pregnancy outcomes were compared between 14 women treated with nutrition therapy and eight women using conventional CD drugs. RESULTS: After 12 weeks, 85.7% (12 of 14) of patients treated with peptide-based formula achieved remission with a significant decrease in the CD activity index (P < .001) and high-sensitivity C-reactive protein level (P = .004). There were no effects of peptide-based formula therapy on pregnancy outcomes compared with conventional CD treatment (P > .05). Among the 12 patients who achieved CD remission with exclusive peptide-based formula therapy, 10 selected to continue total or partial peptide-based formula treatment to maintain CD remission throughout pregnancy. CONCLUSION: Peptide-based formula therapy, without other food intake, may provide a safe and effective alternative to conventional CD drugs to induce disease remission among women during conception and pregnancy.

Maternal tobacco exposure during pregnancy and allergic rhinitis in offspring: A systematic review and meta-analysis.

BACKGROUND: Maternal tobacco exposure during pregnancy is known to cause a potential hazard to the offspring's health. So far, published studies have shown no consistent results with whether tobacco exposure in utero is causally linked to the development of allergic rhinitis in offspring. The aim of this study was to comprehensively evaluate the association between maternal tobacco exposure during pregnancy and allergic rhinitis in offspring by meta-analysis and to provide reference for clinical work. METHODS: Literatures were searched in CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of science and Embase up to September 30,2020. Screening, inclusion, quality assessment, data extraction and data analysis of the literatures were conducted. Meta-analysis was performed with Revman 5.3 and State15.1 software. Odds ratio (OR) and 95%CI were used as observation indicators. RESULTS: We had retrieved 16 articles with 22 independent datasets and 11,49,879 sample size. When all the studies were analyzed together, the results showed that maternal smoking exposure during pregnancy would increase the risk of allergic rhinitis in offspring (OR = 1.13, 95%CI:1.02-1.26), especially maternal passive smoking during pregnancy (OR = 1.39, 95%CI:1.05-1.84). But subgroup analysis showed that maternal active smoking during pregnancy was only significantly associated with offspring allergic rhinitis in cross-sectional studies (OR = 1.24, 95%CI:1.07-1.45) and study done in America study (OR = 1.22, 95%CI:1.05-1.42). CONCLUSIONS: Tobacco exposure during pregnancy could increase the risk of allergic rhinitis in offspring. The importance of avoiding prenatal tobacco exposure should be emphasized more for the health of next generation in the public.

[Reliability of three dimensional CT measurement of glenoid track in patients with recurrent anterior dislocation of shoulder].

OBJECTIVE: To evaluate the reliability and repeatability of three-dimensional (3D)-CT measurement of glenoid track. METHODS: Glenoid and Hill-Sachs bone defects in 60 patients with recurrent anterior dislocation of the unilateral shoulder were evaluated by 3D-CT and analyzed by three independent observers(shoulder orthopedists) according to the Di Giacomo method. These injuries were classified to formulate a surgical protocol. All the patients were repeatedly measured 1 week later. Intraclass correlation coefficient (ICC) and coefficient of variation (COV) were used for reliability analysis. RESULTS: Interobserver reliability was "very good" for both measurements of glenoid diameter and glenoid bone defects, and "good" for measurements of Hill-Sachs interval. Interobserver agreement was high on the assessment of the extent of the glenoid defect, and poor on track/off track assessment of the Hill-Sachs lesion. Intraobserver reliability for measurements of glenoid diameter, glenoid defect, and Hill-Sachs interval was "very good". The COV was 4.1% for glenoid diameter, 4.4% for glenoid defect, and 21.1% for Hill-Sachs interval. CONCLUSION: The reliability and reproducibility of 3D-CT measurements of glenoid bone defects are good, but the assessment of humeral head bone defects shows large variability with poor reliability.

TfOH-promoted synthesis of 4,5-dihydrooxazolo[5,4-c]isoquinolines via formal [3 + 2] cycloaddition of 4-diazoisoquinolin-3-one and benzonitriles.

A facile and efficient method for the synthesis of novel 2-substituted 4-tosyl-4,5-dihydrooxazolo[5,4-c]isoquinolines from 4-diazoisoquinolin-3-ones and nitriles is reported. The reaction proceeded through a TfOH-promoted formal [3 + 2] cycloaddition and the products could be conveniently converted to 2-aryloxazolo[5,4-c]isoquinolines and the subsequent 2-(oxazolo[5,4-c]isoquinolin-2-yl)phenol which emitted bright green light in dilute dichloromethane solution and in solid form as well. Simple operation, metal-free and mild reaction conditions, short reaction time and broad substrate scope are the prominent features of this methodology.

[Sagittal Balance Parameters Correlate with Resorption of the Lumbar Disc Extrusion: Results of a Retrospective Study].

OBJECTIVE: A retrospective study was designed to explore the relationship between the satittal spinopelvic alignment in patients with lumbar disc extrusion and spontaneous resorption. METHODS: From May 2010 to March 2019, referring to NASS evidence-based clinical guidelines, patients with lumbar disc extrusion were enrolled in this retrospective study, according to the degree of herniation size during the follow-up, the patients were divided into two groups: resorption (group R: the herniated disc completely disappeared or the herniation size was grade 1 according to Michgan State University (MSU) classification) and nonresorption (group N: the herniated disc remain unchanged or the herniation size overpass grade 1), spinopelvic parameters (including the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL)) were determined on standing profile radiographs of the lumbar spine and pelvis, and mean values were compared using the multi-factor analysis of variance. RESULTS: This study included 67 patients with lumbar disc extrusion. There were 37 in group R (the average age was 42.6 years), 21 males and 16 females, 13 cases at L 4-5 level and 24 cases at L 5-S 1 level, follow-up 22 months, and 30 in group N (the average age was 40.8 years), 19 males and 11 females, 12 cases at L 4-5 level and 18 cases at L 5-S 1 level, follow-up 21 months, at the follow up time, there symptoms were all satisfactorily relieved. There were no signifcant differences in age, gender, smoking history, chronic medical history, prominent segmnet, MSU classification, follow up time and other baseline conditions between two groups ( P>0.05). At the follow-up, in group R, all 30 cases of sagittal displaced disc disappeared, the herniated disc changed from the initial MSU classification of grade 2 in 19 cases and grade 3 in 18 cases to the post-absorption residual disc, which were limited to grade 1; in group N, 20 cases of sagittal displaced disc reduced to 14 cases, the herniated disc changed from the initial MSU classification of grade 2 in 21 cases and grade 3 in 9 cases to grade 2 in 27 cases and grade 3 in 3 cases. There was no significant difference in spinopelvic parameters between the two groups before the treatment ( P>0.05). At the follow-up, there was no significant difference in PI between the two groups ( P>0.05); the SS and LL in group R were bigger than those in group N, the PT in group R was smaller than that in group N, and the difference was statistically significant ( P<0.05). Compared within the same group, before treatment and follow-up, there were no significant differences in PI, SS and PT in group R, but a bigger LL ( P<0.05); no significant differences in all the parameters in group N were found. CONCLUSION: Resorption may result in pinopelvic parameter changes, which suggest that the lumbar spine is better at cushioning against load, reducing the disc pressure, and leading to resorption of the herniated disc.

Preparation of 4-Diazoisoquinolin-3-ones via Dimroth Rearrangement and Their Extension to 4-Aryltetrahydroisoquinolin-3-ones.

4-Diazoisoquinolin-3-ones were prepared efficiently via TBAB-promoted rearrangement of 4-diazoisochroman-3-imines under mild reaction conditions. The resulted 4-diazoisoquinolin-3-ones could be conveniently applied for the synthesis of 4-aryltetrahydroisoquinolin-3-ones either by the TfOH-catalyzed reaction with electron-rich arenes or by the BF3-promoted reaction with aryl aldehydes.

Current diagnosis and management of Crohn's disease in China: results from a multicenter prospective disease registry.

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

Synthetic N-terminal coding sequences for fine-tuning gene expression and metabolic engineering in Bacillus subtilis.

N-terminal coding sequences (NCSs) of genes significantly influence gene expression at the translation level and are important for fine-tuning gene expression in bacteria, however, engineering NCSs to fine-tune metabolic pathways is challenging. Here, we developed a statistics-guided native and synthetic NCSs engineering approach to fine-tune gene expression in the industrially important microorganism Bacillus subtilis. This method is based on experimentally characterizing and statistically analyzing 96 rationally selected NCSs from B. subtilis endogenous genes. These NCSs exhibited a magnitude difference of greater than 4 orders in their ability to drive gene expression in 4 different dynamic patterns, including growth-coupled, growth-delayed, consistent expression, and inhibitory patterns. Synthetic and native NCSs were used to fine-tune expression of key enzymes, identified via pathway analysis and kinetic modeling, in the biosynthetic pathway of the useful nutraceutical N-acetylneuraminic acid (NeuAc). We observed a 3.21-fold improvement in NeuAc biosynthesis, indicating that NCSs can provide a synthetic biology toolbox to fine-tune gene expression for metabolic engineering.