Metabolic engineering of Halomonas bluephagenesis for production of five carbon molecular chemicals derived from L-lysine.

5-Aminovaleric acid (5-AVA), 5-hydroxyvalerate (5HV), copolymer P(3HB-co-5HV) of 3-hydroxybutyrate (3HB) and 5HV were produced from L-lysine as a substrate by recombinant Halomonas bluephagenesis constructed based on codon optimization, deletions of competitive pathway and L-lysine export protein, and three copies of davBA genes encoding L-lysine monooxygenase (DavB) and 5-aminovaleramide amidohydrolase (DavA) inserted into its genome to form H. bluephagenesis YF117ΔgabT1+2, which produced 16.4 g L-1 and 67.4 g L-1 5-AVA in flask cultures and in 7 L bioreactor, respectively. It was able to de novo synthesize 5-AVA from glucose by L-lysine-overproducing H. bluephagenesis TD226. Corn steep liquor was used instead of yeast extract for cost reduction during the 5-AVA production. Using promoter engineering based on Pporin mutant library for downstream genes, H. bluephagenesis YF117 harboring pSEVA341-Pporin42-yqhDEC produced 6 g L-1 5HV in shake flask growth, while H. bluephagenesis YF117 harboring pSEVA341-Pporin42-yqhDEC-Pporin278-phaCRE-abfT synthesized 42 wt% P(3HB-co-4.8 mol% 5HV) under the same condition. Thus, H. bluephagenesis was successfully engineered to produce 5-AVA and 5HV in supernatant and intracellular P(3HB-co-5HV) utilizing L-lysine as the substrate.

Intelligent Compound Fault Diagnosis of Roller Bearings Based on Deep Graph Convolutional Network.

The high correlation between rolling bearing composite faults and single fault samples is prone to misclassification. Therefore, this paper proposes a rolling bearing composite fault diagnosis method based on a deep graph convolutional network. First, the acquired raw vibration signals are pre-processed and divided into sub-samples. Secondly, a number of sub-samples in different health states are constructed as graph-structured data, divided into a training set and a test set. Finally, the training set is used as input to a deep graph convolutional neural network (DGCN) model, which is trained to determine the optimal structure and parameters of the network. A test set verifies the feasibility and effectiveness of the network. The experimental result shows that the DGCN can effectively identify compound faults in rolling bearings, which provides a new approach for the identification of compound faults in bearings.

Learning dispatching rules via novel genetic programming with feature selection in energy-aware dynamic job-shop scheduling.

The incorporation of energy conservation measures into production efficiency is widely recognized as a crucial aspect of contemporary industry. This study aims to develop interpretable and high-quality dispatching rules for energy-aware dynamic job shop scheduling (EDJSS). In comparison to the traditional modeling methods, this paper proposes a novel genetic programming with online feature selection mechanism to learn dispatching rules automatically. The idea of the novel GP method is to achieve a progressive transition from exploration to exploitation by relating the level of population diversity to the stopping criteria and elapsed duration. We hypothesize that diverse and promising individuals obtained from the novel GP method can guide the feature selection to design competitive rules. The proposed approach is compared with three GP-based algorithms and 20 benchmark rules in the different job shop conditions and scheduling objectives considered energy consumption. Experiments show that the proposed approach greatly outperforms the compared methods in generating more interpretable and effective rules. Overall, the average improvement over the best-evolved rules by the other three GP-based algorithms is 12.67%, 15.38%, and 11.59% in the meakspan with energy consumption (EMS), mean weighted tardiness with energy consumption (EMWT), and mean flow time with energy consumption (EMFT) scenarios, respectively.

Reliability modelling and evaluating of wind turbine considering imperfect repair.

To model and evaluate the reliability of wind turbine (WT) under imperfect repair, an improved Log-linear Proportional Intensity Model (LPIM)-based method was proposed. Initially, using the three-parameter bounded intensity process (3-BIP) as the benchmark failure intensity function of LPIM, an imperfect repair effect-aware WT reliability description model was developed. Among them, the 3-BIP was used to describe the evolution process of the failure intensity in the stable operation stage with running time, while the LPIM reflected the repair effect. Second, the estimation problem for model parameters was transformed into a minimum solution problem for a nonlinear objective function, which was then solved using the Particle Swarm Optimization algorithm. The confidence interval of model parameters was finally estimated using the inverse Fisher information matrix method. Key reliability indices interval estimation based on the Delta method and point estimation was derived. The proposed method was applied to a wind farm's WT failure truncation time. The proposed method has a higher goodness of fit based on verification and comparison. As a result, it can bring the evaluated reliability closer to engineering practice.

Case report: Acute ischemic stroke caused by intracranial artery dissection in a patient with skull fractures.

The intracranial artery dissection (IAD) is an uncommon but life-threatening disease. The IAD would develop a significant cerebral infarction due to unrecognized contrecoup brain injury. We report a 53-year-old man fell to develop blunt cerebrovascular injuries (BCVIs) more than 2 months ago. During his rehabilitation, he often had a transient left headache and underwent short-term right limb weakness twice, but he did not care. He was hospitalized again because of suffering right limb weakness for more than 4 h. The brain computed tomography angiography (CTA) showed subtotal occlusion of the left middle cerebral artery M1 segment, and the vascular morphology displayed the IAD. The patient was then treated with balloon dilation and a self-expanding stent. This case highlights that IAD may show delayed onset with no initial typical symptom. By early detecting of abnormal signs and symptoms, serious traumatic brain injury may be avoided.

Engineering an oleic acid-induced system for Halomonas, E. coli and Pseudomonas.

Ligand-induced system plays an important role for microbial engineering due to its tunable gene expression control over timings and levels. An oleic acid (OA)-induced system was recently constructed based on protein FadR, a transcriptional regulator involved in fatty acids metabolism, for metabolic control in Escherichia coli. In this study, we constructed a synthetic FadR-based OA-induced systems in Halomonas bluephagenesis by hybridizing the porin promoter core region and FadR-binding operator (fadO). The dynamic control range was optimized over 150-fold, and expression leakage was significantly reduced by tuning FadR expression and positioning fadO, forming a series of OA-induced systems with various expression strengths, respectively. Additionally, ligand orthogonality and cross-species portability were also studied and showed highly linear correlation among Halomonas spp., Escherichia coli and Pseudomonas spp. Finally, OA-induced systems with medium- and small-dynamic control ranges were employed to dynamically control the expression levels of morphology associated gene minCD, and monomer precursor 4-hydroxybutyrate-CoA (4HB-CoA) synthesis pathway for polyhydroxyalkanoates (PHA), respectively, in the presence of oleic acid as an inducer. As a result, over 10 g/L of poly-3-hydroxybutyrate (PHB) accumulated by elongated cell sizes, and 6 g/L of P(3HB-co-9.57 mol% 4HB) were obtained by controlling the dose and induction time of oleic acid only. This study provides a systematic approach for ligand-induced system engineering, and demonstrates an alternative genetic tool for dynamic control of industrial biotechnology.

A combined quality evaluation method that integrates chemical constituents, appearance traits and origins of raw Rehmanniae Radix pieces.

The quality control of Chinese herbal medicine is a current challenge for the internationalization of traditional Chinese medicine. Traditional quality evaluation methods lack quantitative analysis, while modern quality evaluation methods ignore the origins and appearance traits. Therefore, an integrated quality evaluation method is urgent in need. Raw Rehmanniae Radix (RRR) is commonly used in Chinese herbal medicine. At present, much attention has been drwan towards its quality control, which however is limited by the existing quality evaluation methods. The present study was designed to establish a comprehensive and practical method for the quality evaluation and control of RRR pieces based on its chemical constituents, appearance traits and origins. Thirty-three batches of RRR pieces were collected from six provinces, while high-performance liquid chromatography (HPLC) was applied to determine the following five constituents, including catalpol, rehmannioside A, rehmannioside D, leonuride and verbascoside in RRR pieces. Their appearance traits were quantitatively observed. Furthermore, correlation analysis, principal components analysis (PCA), cluster analysis and t-test were performed to evaluate the qualities of RRR pieces. These batches of RRR pieces were divided into three categories: samples from Henan province, samples from Shandong and Shanxi provinces, and those from other provinces. Furthermore, the chemical constituents and appearance traits of RRR pieces were significantly different from diverse origins. The combined method of chemical contituents, appearance traits and origins can distinguish RRR pieces with different qualities, which provides basic reference for the quality control of Chinese herbal medicine.

Proof-of-principle demonstration of measurement-device-independent quantum key distribution based on intrinsically stable polarization-modulated units.

The experimental demonstration of measurement-device-independent quantum key distribution (MDI-QKD) has been widely demonstrated. Thus far, several experimental groups have implemented polarization encoding MDI-QKD but with manual polarization controllers, or polarization modulators that make circular polarization states unstable. Here, we apply an intrinsically stable polarization-modulated unit (PMU) to MDI-QKD so that Alice and Bob can modulate four BB84 polarization states, all of which can be kept stable from even the harsh environment. Moreover, our PMU can provide two operational polarization encoding modes suitable to different application scenarios. A proof-of-principle demonstration of MDI-QKD based on our PMU is implemented with an interference visibility of 46.6%, an average quantum bit error rate of 1.49% for the Z basis and the secure key rate of 4.25 × 10-6 bits per pulse. The proposed study is helpful for building polarization encoding MDI-QKD systems with better stability.

Purification and characterization of a thaumatin-like protein-1 with polyphenol oxidase activity found in Prunus mume.

Thaumatin-like protein-1 (TLP-1), a protein displaying high polyphenol oxidase (PPO) action and a member of the pathogenesis-related (PR) protein family, has a considerable influence on the enzymatic browning of Prunus mume (Chinese plum). In this assay, TLP-1 was identified and extracted from Prunus mume to investigate the protein's properties and better understand its contribution to the fruit's browning during storage or processing. The extracted TLP-1 was purified to apparent homogeneity using a procedure involving citrate phosphate buffer solution (CPBS) extraction, (NH4)2SO4 precipitation, dialysis in a cellulose bag, and ion exchange chromatography using a DEAE Sepharose Fast Flow column, while a Sephadex G-75 column was employed to facilitate gel filtration chromatography. Moreover, the enzyme was characterized in terms of its optimal pH and stability, isoelectric point (pI), molecular weight, optimal temperature and stability, enzyme kinetic parameters and substrate specificity, as well as inhibitor stability. This study indicated that the pI and molecular weight of TLP-1 was approximately 4.4 and 28 kDa, respectively, while 30 °C and 7.5 represented the respective optimal temperature and pH level for PPO catalysis. TLP-1 showed high affinity to catechol and pyrogallol, with K m values of 24.40 mM and 26.23 mM, respectively. Sodium bisulfite significantly inhibited TLP-1 activity. These findings on the properties of TLP-1 can contribute significantly to the search for ways to minimize the losses caused by fruit browning during the storage and processing of Prunus mume.

Constrained likelihood for reconstructing a directed acyclic Gaussian graph.

Directed acyclic graphs are widely used to describe directional pairwise relations. Such relations are estimated by reconstructing a directed acyclic graph's structure, which is challenging when the ordering of nodes of the graph is unknown. In such a situation, existing methods such as the neighbourhood and search-and-score methods have high estimation errors or computational complexities, especially when a local or sequential approach is used to enumerate edge directions by testing or optimizing a criterion locally, as a local method may break down even for moderately sized graphs. We propose a novel approach to simultaneously identifying all estimable directed edges and model parameters, using constrained maximum likelihood with nonconvex constraints. We develop a constraint reduction method that constructs a set of active constraints from super-exponentially many constraints. This, coupled with an alternating direction method of multipliers and a difference convex method, permits efficient computation for large-graph learning. We show that the proposed method consistently reconstructs identifiable directions of the true graph and achieves the optimal performance in terms of parameter estimation. Numerically, the method compares favourably with competitors. A protein network is analysed to demonstrate that the proposed method can make a difference in identifying the network's structure.

[Origin of lifting and lowering theory and its herb pair study].

Lifting and lowering theory is one of the important basis for guiding clinical medication. Through the study of ancient books and literature, we learned that lifting and lowering theory was originated in Huangdi Neijing, practiced more in the Shanghan Zabing Lun, established in Yixue Qiyuan, and developed in Compendium of Materia Medica and now. However, lifting and lowering theory is now mostly stagnated in the theoretical stage, with few experimental research. In the clinical study, the guiding role of lifting and lowering theory to prescriptions?mainly includes opposite?role?of lift and lower medicine property, mutual promotion of lift and lower medicine property, main role of lift medicine property and main role of lower medicine property. Under the guidance of lifting and lowering theory, the herb pair compatibility include herb combination of lift medicine property, herb combination of lift and lower medicine property and herb combination of lower medicine property. Modern biological technology was used in this study to carry out experimental research on the lifting and lowering theory, revealing the scientific connotation of it, which will help to promote clinical rational drug use.

[Analysis of historical origin and standardization system construction of Citri Grandis Exocarpium].

To understand the history development and changes of Citri Grandis Exocarpium and initially establish its standard system after exploring the historical origins and modern development of Citri Grandis Exocarpium. In CNKI, Wanfang database and other academic search platforms were searched for literature on Citri Grandis Exocarpium and Chinese medicine standard system； the books related to its modern cultivation techniques and processing technology were also accessed, and after combining with the actual situation analysis, the prospective design of the standard system of Citri Grandis Exocarpium was finally established with research conclusion. The earliest records of the Citri Grandis Exocarpium were documented in the Northern and Southern Dynasties, but its medicinal value was discovered in the Song Dynasty. Its drug use was developed on the basis of Jupi（orange peel） and Citri Exocarpium Rubrum. In 21st century, a number of large-scale, intensive Citri Grandis Exocarpium bases have been formed due to high price, good planting efficiency, and rapid growth of cultivation areas. The standard system includes the technical specifications of seed selection and seedling cultivation of Citri Grandis Exocarpium, technical norms of cultivation, technical specifications of fertilizing and weeding, technical specifications of irrigation and drainage, technical standard of pest and disease control, standard of medicinal materials grade, standard of processing technology of sliced pieces and the quality standard of slices, etc.

Effects of Mahuang (Herba Ephedra Sinica) and Wuweizi (Fructus Schisandrae Chinensis) medicated serum on chemotactic migration of alveolar macrophages and inters regions macrophages in rats.

OBJECTIVE: To observe the effects of serum containing Mahuang (Herba Ephedra Sinica) or Wuweizi (Fructus Schisandrae Chinensis) on the migration of alveolar macrophages (AM) and interstitial macrophages (IM) from normal rats, and to analyze and compare the mechanisms leading to cell migration differences. METHODS: Rats were randomly divided into three groups: Mahuang (Herba Ephedra Sinica), Wuweizi (Fructus Schisandrae Chinensis), and blank serum. After treatment with the herbs, serum was extracted from the rats. AM and IM were isolated from normal rats and cultured. The effects of Mahuang (Herba Ephedra Sinica) and Wuweizi (Fructus Schisandrae Chinensis) medicated serum on normal rat AM and IM chemotactic migration were determined by transwell assays. The CC chemokine receptor (CCR) 2, CCR5, voltage-gated Kvl. 3 K+ channel (Kv1. 3), and voltage-gated Kvl. 5 K+ channel (Kv1. 5) protein levels were analyzed by western blotting. RESULTS: The migration quantities of AM and IM in the Mahuang (Herba Ephedra Sinica) and Wuweizi (Fructus Schisandrae Chinensis) medicated serum groups were significantly higher than those in the blank serum group (P < 0.01). Compared with the Wuweizi (Fructus Schisandrae Chinensis) medicated serum group, the migration quantity of cultured rat AM in the Mahuang (Herba Ephedra Sinica) medicated serum group was significantly increased (P < 0.01). Meanwhile, compared with the Mahuang (Herba Ephedra Sinica) medicated serum group, the migration quantity of cultured rat IM in the Wuweizi (Fructus Schisandrae Chinensis) medicated serum group was significantly increased (P < 0.01). CCR2, CCR5, Kv1. 3, and Kv1. 5 proteins were expressed on the AM cell surface, and showed significantly higher expression in the Mahuang (Herba Ephedra Sinica) medicated serum group compared with the Wuweizi (Fructus Schisandrae Chinensis) medicated serum group. In contrast, CCR5, Kv1.3, and Kv1.5 proteins were expressed on the IM cell surface, and showed significantly higher expression in the Wuweizi (Fructus Schisandrae Chinensis) medicated serum group compared with the Mahuang (Herba Ephedra Sinica) medicated serum group. CONCLUSION: Mahuang (Herba Ephedra Sinica) and Wuweizi (Fructus Schisandrae Chinensis) can promote AM and IM migration ability, with Mahuang (Herba Ephedra Sinica) targeting AM more apparently and Wuweizi (Fructus Schisandrae Chinensis) targeting IM more apparently. The mechanism may be that, by stimulating cells, Mahuang (Herba Ephedra Sinica) and Wuweizi (Fructus Schisandrae Chinensis) promote expression of CCR2 and CCR5 receptors on the AM and IM cell surface, which pass signals to Kvl.3 and Kvl.5 ion channels, leading to changes in the cytoskeleton, and ultimately promoting chemotactic cell migration.

The Impact of Excluding Trials from Network Meta-Analyses - An Empirical Study.

Network meta-analysis (NMA) expands the scope of a conventional pairwise meta-analysis to simultaneously compare multiple treatments, which has an inherent appeal for clinicians, patients, and policy decision makers. Two recent reports have shown that the impact of excluding a treatment on NMAs can be substantial. However, no one has assessed the impact of excluding a trial from NMAs, which is important because many NMAs selectively include trials in the analysis. This article empirically examines the impact of trial exclusion using both the arm-based (AB) and contrast-based (CB) approaches, by reanalyzing 20 published NMAs involving 725 randomized controlled trials and 449,325 patients. For the population-averaged absolute risk estimates using the AB approach, the average fold changes across all networks ranged from 1.004 (with standard deviation 0.004) to 1.072 (with standard deviation 0.184); while the maximal fold changes ranged from 1.032 to 2.349. In 12 out of 20 NMAs, a 1.20-fold or larger change is observed in at least one of the population-averaged absolute risk estimates. In addition, while excluding a trial can substantially change the estimated relative effects (e.g., log odds ratios), there is no systematic difference in terms of changes between the two approaches. Changes in treatment rankings are observed in 7 networks and changes in inconsistency are observed in 3 networks. We do not observe correlations between changes in treatment effects, treatment rankings and inconsistency. Finally, we recommend rigorous inclusion and exclusion criteria, logical study selection process, and reasonable network geometry to ensure robustness and generalizability of the results of NMAs.

[National physician master Jin Shiyuan's dispensing technology of Rehmanniae Radix Praeparata based on Li Shizhen's pharmaceutical academic thought].

To collect the historical origin, processing methods and clinical application of Rehmanniae Radix Preparata in Compendium of Materia Medica, compare and analyze the theoretical knowledge and relevant practical operation of national physician master Jin Shiyuan, which is beneficial for the inheritance and development of Rehmanniae Radix Preparata's clinical dispensing technology. In the analysis process, CNKI was searched with "Rehmanniae Radix Preparata", "Processing method", "Clinical application" "Li Shizhen", "Jin Shiyuan", and "Dispensing technology" as keywords. In addition, Shennong's Herbal Classic, Bencao Tujing (illustrated Classics of Materia Medica), Compendium of Materia Medica, Jingyue Quanshu (Jingyue's Complete Works) and related ancient books were accessed systematically to summarize the historical change of processing methods and efficacy of Rehmanniae Radix Praeparata. Professor Jin Shiyuan emphasizes the clinical dispensing technology of Rehmanniae Radix Praeparata, including its nature identification technology, clinical processing technology, prescription audit technology, prescription coping technology, drug delivery technology, clinical decocting technology, purchasing management technology as well as storage, maintenance and supply technology. Through the collation and research, it was confirmed that historical origin, processing methods and clinical application of Rehmanniae Radix Preparata were recorded in details in Compendium of Materia Medica. Steaming method of Rehmanniae Radix Preparata was originated from Synopsis of Golden Chamber. Li Shizhen attached great importance to the processing method of "steaming and drying alternatively for nine times" for Rehmanniae Radix Preparata, and differentiated it from Radix Rehmanniae Recen and fresh rehmannia root in clinical applications. Professor Jin Shiyuan has developed and improved the clinical dispensing technology of Rehmanniae Radix Praeparata, and carried forward the essence of Li Shizhen's pharmaceutical academic thought with his own proficient knowledge structure in medicine, providing scientific pharmaceutical service for clinical application of Rehmanniae Radix Preparata in future.

[National physician master Jin Shiyuan's dispensing technology of Aconiti Lateralis Radix Praeparata based on Li Shizhen's pharmaceutical academic thought].

To collect Li Shizhen's experience in Aconiti Lateralis Radix Praeparata identification and clinical application, compare and analyze national physician master Jin Shiyuan's practical operation and theoretical knowledge, which is beneficial for the inheritance and improvement of Aconiti Lateralis Radix Praeparata clinical dispensing technology. In the analysis process, CNKI, Wanfang and other databases were searched with "Aconiti Lateralis Radix Praeparata", "Li Shizhen", "pharmacological method state theory" "Jin Shiyuan" and "Chinese medicine dispensing technology" as the key words. In addition, Treatise on Febrile Disease, Compendium of Materia Medica, Chinese Pharmacopoeia(2015 edition), Notes to Medical Professions(Yi Zong Shuo Yue), and other medicine books were accessed to summarize the processing methods and decoction dosage of Aconiti Lateralis Radix Praeparata in both ancient and modern medicine, and in consideration of technical research and practice operation, Li Shizhen's description of Aconiti Lateralis Radix Praeparata and Professor Jin Shiyuan's research on Aconiti Lateralis Radix Praeparata dispensing technology were analyzed and collected. Li Shizhen recorded the nature identification and clinical application of Aconiti Lateralis Radix Praeparata by using pharmacological method state theory in Compendium of Materia Medica. National physician master Jin Shiyuan carries forward the essence of Li Shizhen's pharmaceutical academic thought with his own proficient knowledge structure in medicine, providing scientific pharmaceutical service for clinical application of Aconiti Lateralis Radix Praeparata Professor. Jin Shiyuan put forward the dispensing technology for the first time, including nature identification technology, clinical processing technology, clinical decocting technology, prescription coping technology, and class specifications of Aconiti Lateralis Radix Praeparata. In this paper, Aconiti Lateralis Radix Praeparata was used as an example to analyze the key dispensing technology of traditional Chinese medicine, and apply the key dispensing technology of traditional Chinese medicine in various commonly used Chinese medicines in the future.

Maximum Likelihood Estimation Over Directed Acyclic Gaussian Graphs.

Estimation of multiple directed graphs becomes challenging in the presence of inhomogeneous data, where directed acyclic graphs (DAGs) are used to represent causal relations among random variables. To infer causal relations among variables, we estimate multiple DAGs given a known ordering in Gaussian graphical models. In particular, we propose a constrained maximum likelihood method with nonconvex constraints over elements and element-wise differences of adjacency matrices, for identifying the sparseness structure as well as detecting structural changes over adjacency matrices of the graphs. Computationally, we develop an efficient algorithm based on augmented Lagrange multipliers, the difference convex method, and a novel fast algorithm for solving convex relaxation subproblems. Numerical results suggest that the proposed method performs well against its alternatives for simulated and real data.

[Influences of diagnostic modes on an early diagnosis of colorectal cancer].

OBJECTIVE: To explore the influences of diagnostic modes of colorectal cancer (CRC) on an early diagnosis of CRC. METHODS: A total of 405 cases were randomly collected from 1798 CRC patients registered at our hospital from January 2000 to December 2010. A retrospective chart review was undertaken for all identified cases. Besides the demographics and tumor features, TNM stage was obtained from medical records and pathological forms. Other collected data were as follows: (1) Type of clinical examinations leading to diagnosis. (2) Diagnostic duration: including patient duration (period from initial symptoms to consulting a doctor and hospitalization duration (period from patient first seeing a doctor to a confirmed CRC case). (3) Diagnostic delay and its rate: diagnostic delay was identified as the diagnostic duration of over 30 days. We compared the different delay periods of 31 - 60, 61 - 90, 91 - 150 and > 150 days and its corresponding tumor stages at diagnosis. (4) Misdiagnosis and its rate: that CRC subjects were diagnosed and treated as other diseases for at least 30 days was identified as misdiagnosis. The t and Mann-Whitney U tests were performed for the quantitative data and χ(2) test for the qualitative data. RESULTS: Among the study subjects, 67.2% (270/402) CRC cases were examined by colonoscopy, 17.4 % (70/402) cases by CT scan or B ultrasound. The median diagnostic duration of CRC was 90 days (25% percentile: 40 days, 75% percentile: 210 days). The median patient duration was 30 days and median hospital duration 10 days. The overall misdiagnostic rate of CRC was 27.9% (112/401), higher (39.7%, 48/121) in right sited CRC than in left sited CRC (22.9%, 63/275) (χ(2) = 11.7, P = 0.00). 77.7% (313/403) cases had > 30 days diagnostic delay, 50.8% (156/307) delay attributable to the patients, while 29.0% (89/307) attributable to hospitals and 20.2% (62/307) attributable to both. The diagnostic duration of early-stage CRC and advanced-stage CRC appeared to be in the same length. On the other hand, no difference of TNM stage at the initial diagnosis was found in groups with different diagnostic durations of 31 - 60, 61 - 90, 91 - 150 and > 150 days (all P > 0.05). CONCLUSION: Colonoscopy is the most effective in the diagnosis of CRC. The median diagnostic time of CRC is 90 days. The phenomenon of its diagnostic delay often occurs. However, the delay is not a major cause for its advanced stage and a poor outcome. Its inherent biological characteristics may be more important.