Outcomes of robot-assisted versus video-assisted mediastinal mass resection during the initial learning curve.

To compare the learning curve of mediastinal mass resection between robot-assisted surgery and thoracoscopic surgery. Retrospective perioperative data were collected from 160 mediastinal mass resection cases. Data included 80 initial consecutive video-assisted thoracoscopic surgery (VATS) resection cases performed from February 2018 to February 2020 and 80 initial consecutive robotic-assisted thoracic surgery (RATS) resection cases performed from March 2020 to March 2023. All cases were operated on by a thoracic surgeon. The clinical characteristics and perioperative outcomes of the two groups were compared. The operation time in both the RATS group and VATS group was analyzed using the cumulative sum (CUSUM) method. Based on this method, the learning curves of both groups were divided into a learning period and mastery period. The VATS group and the RATS group crossed the inflection point in the 27th and 21st case, respectively. Subsequently, we found that the learning period was longer than the mastery period with statistically significant differences in terms of the operating time, and postoperative hospital stay in the VATS group and the RATS group. A certain amount of VATS experience can shorten the learning curve for RATS.

Pulmonary vagus nerve transection for chronic cough after video-assisted lobectomy: a randomized controlled trial.

BACKGROUND: Chronic cough is common after lobectomy. Vagus nerves are part of the cough reflex. Accordingly, transection of the pulmonary branches of vagus nerve may prevent chronic cough. And there are no clear recommendations on the management of the pulmonary branches of vagus in any thoracic surgery guidelines. METHODS: This is a single-center, randomized controlled trial. Adult patients undergoing elective video-assisted thoracoscopic lobectomy and lymphadenectomy were randomized at a 1:1 ratio to undergo a sham procedure (control group) or transection of the pulmonary branches of the vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch of the vagus nerve. The primary outcome was the rate of chronic cough, as assessed at 3 months after surgery in the intent-to-treat population. RESULTS: Between 1 February 2020 and 1 August 2020, 116 patients (59.6±10.1 years of age; 45 men) were randomized (58 in each group). All patients received designated intervention. The rate of chronic cough at 3 months was 19.0% (11/58) in the vagotomy group versus 41.4% (24/58) in the control group (OR=0.332, 95% CI: 0.143-0.767; P =0.009). In the 108 patients with 2-year assessment, the rate of persistent cough was 12.7% (7/55) in the control and 1.9% (1/53) in the vagotomy group ( P =0.032). The two groups did not differ in postoperative complications and key measures of pulmonary function, for example, maximal voluntary ventilation, diffusing capacity of the lungs for carbon monoxide, and forced expiratory volume. CONCLUSION: Transecting the pulmonary branches of vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch decreased the rate of chronic cough without affecting pulmonary function in patients undergoing video-assisted lobectomy and lymphadenectomy.

HOMER3 promotes non-small cell lung cancer growth and metastasis primarily through GABPB1-mediated mitochondrial metabolism.

Cancer metabolism has emerged as a major target for cancer therapy, while the state of mitochondrial drugs has remained largely unexplored, partly due to an inadequate understanding of various mitochondrial functions in tumor contexts. Here, we report that HOMER3 is highly expressed in non-small cell lung cancer (NSCLC) and is closely correlated with poor prognosis. Lung cancer cells with low levels of HOMER3 are found to show significant mitochondrial dysfunction, thereby suppressing their proliferation and metastasis in vivo and in vitro. At the mechanistic level, we demonstrate that HOMER3 and platelet-activating factor acetylhydrolase 1b catalytic subunit 3 cooperate to upregulate the level of GA-binding protein subunit beta-1 (GABPB1), a key transcription factor involved in mitochondrial biogenesis, to control mitochondrial inner membrane genes and mitochondrial function. Concurrently, low levels of HOMER3 and its downstream target GABPB1 led to mitochondrial dysfunction and decreased proliferation and invasive activity of lung cancer cells, which raises the possibility that targeting mitochondrial synthesis is an important and promising therapeutic approach for NSCLC.

Evaluation of pain levels treated by the distal end of the hook-wire positioning needle: A randomized controlled study.

BACKGROUND: Severe pain can be expected among adult patients undergoing hook-wire CT-guided localization of pulmonary nodules. We compared varying pain degrees between two different treatment techniques. METHODS: Data from 100 patients who underwent hook-wire puncture localization under preoperative CT between May 2022 and October 2022 were prospectively reviewed. Using the random number table method, the patients were assigned to an observation and control group in a 1:1 ratio. In the observation group (n = 50), the external part of the hook-wire positioning needle was cut off; in the control group (n = 50), the external portion of the needle was bent. Static pain scores were measured using the visual analog scale (VAS) at 30 min, 1, and 2 h post localization for patients. RESULTS: No significant differences were present between the two groups in terms of patient age, sex, nodule size, and nodule location. The observation group had lower VAS scores at 30 min (2.57 ± 1.38 vs. 3.51 ± 1.87 p = 0.005), 1 h (2.43 ± 1.14 vs. 3.33 ± 1.76 p = 0.003), and 2 h (2.41 ± 1.12 vs. 3.17 ± 1.74 p = 0.011) after localization. Moreover, the pain level did not gradually worsen in either group. Both groups had a 100% localization success rate. There was no statistically significant difference (p = 0.431) in the localized complication incidences between the two groups. CONCLUSIONS: We found both approaches for handling the hook-wire extending outside the chest to be safe and effective. However, cutting off the hook-wire extending outside the chest is associated with lesser pain. Moreover, pain severity does not worsen with time after localization.

Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: a large cohort retrospective study.

Purpose: It has been reported that breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2) might be a distinct subtype of BC. However, the prognostic effect of low HER2 expression on BC patients remains controversial. We aim to conduct this single-institution retrospective analysis to assess HER2-low-positive BC outcomes in Chinese women and the prognostic role of TILs in HER2-low-positive early-stage BC. Method: We retrospectively enrolled 1,763 BC patients treated in a single institution from 2017 to 2018. TILs are regarded as continuous variables and are divided into low TILs (≤10%) and high TILs (>10%) for statistical analysis. Univariate and multivariable Cox proportional hazards regression models were used to test the associations between TILs and disease-free survival (DFS) with adjustment for clinicopathologic characteristics. Result: High TIL levels (>10%) were associated with tumor size (>2 cm, p = 0.042), age at diagnosis (p = 0.005), Ki-67 index (>25%; p <0.001), HR (hormone receptor) status (positive, p <0.001), advanced pathological stage (p = 0.043), subtype (p <0.001), and HER2 status (p <0.001). The Kaplan-Meier analysis indicated that no significant difference in DFS (p = 0.83) could be found between HER2-positive, HER2-low-positive, and HER2-0 BC. The DFS of HER2-low-positive BC and HER2-nonamplified BC with high levels of TILs was statistically better than that of patients with low levels of TILs (p = 0.015; p = 0.047). In HER2-low-positive BC patients with high TIL levels (>10%), DFS was significantly improved in both the univariate (HR = 0.44, 95% CI 0.22-0.87, P = 0.018) and multivariate (HR = 0.47, 95% CI 0.23-0.95, P = 0.035) Cox models. For further subgroup analysis, HR (+)/HER2-low-positive BC with high TIL (>10%) levels was associated with improved DFS in both the univariate (HR = 0.41, 95% CI 0.19-0.90, P = 0.025) and multivariate (HR = 0.42, 95% CI 0.19-0.93, P = 0.032) Cox models. The HR (-)/HER2-0 BC with high TIL (>10%) level was not statistically significant in the univariate Cox model, but it was statistically significant in the multivariate (HR = 0.16, 95% CI 0.28-0.96, P = 0.045) Cox model. Conclusion: Among early-stage BC, no significant survival difference could be found between the HER2-positive, HER2-low-positive, and HER2-0 cohorts. High levels of TILs were significantly associated with improved DFS in HER2-low-positive patients, especially in the HR (+)/HER2-low-positive subtype.

Mace-Like Plasmonic Au-Pd Heterostructures Boost Near-Infrared Photoimmunotherapy.

Photoimmunotherapy, with spatiotemporal precision and noninvasive property, has provided a novel targeted therapeutic strategy for highly malignant triple-negative breast cancer (TNBC). However, their therapeutic effect is severely restricted by the insufficient generation of tumor antigens and the weak activation of immune response, which is caused by the limited tissue penetration of light and complex immunosuppressive microenvironment. To improve the outcomes, herein, mace-like plasmonic AuPd heterostructures (Au Pd HSs) have been fabricated to boost near-infrared (NIR) photoimmunotherapy. The plasmonic Au Pd HSs exhibit strong photothermal and photodynamic effects under NIR light irradiation, effectively triggering immunogenic cell death (ICD) to activate the immune response. Meanwhile, the spiky surface of Au Pd HSs can also stimulate the maturation of DCs to present these antigens, amplifying the immune response. Ultimately, combining with anti-programmed death-ligand 1 (α-PD-L1) will further reverse the immunosuppressive microenvironment and enhance the infiltration of cytotoxic T lymphocytes (CTLs), not only eradicating primary TNBC but also completely inhibiting mimetic metastatic TNBC. Overall, the current study opens a new path for the treatment of TNBC through immunotherapy by integrating nanotopology and plasmonic performance.

CT-guided percutaneous transthoracic needle biopsy (PTNB): A thoracic surgeon's learning curve and experience summary.

BACKGROUND: Few studies have investigated the learning process of percutaneous transthoracic needle biopsy (PTNB). Here, we aimed to evaluate the number of cases required to achieve proficiency by plotting the learning curve of PTNB. METHODS: Data were collected from 94 consecutive patients who underwent computed tomography-guided PTNB by a thoracic surgeon at the Affiliated Hospital of Xuzhou Medical University between May 2021 and February 2022. The data collected included patient information, relevant examination results, intraoperative parameters, postoperative complications, and diagnostic results. RESULTS: The inflection points of the cumulative sum curve were around cases 13 and 24, according to which three phases were identified, including phase I, phase II, and phase III. A significant downtrend was observed regarding operative time (phase I, 26.53 ± 9.13 min vs. phase III, 18.42 ± 4.29 min, p < 0.05), rate of false-negative (phase I, 15.4% vs. phase III, 5.7%; p < 0.05), rate of pneumothorax (phase I, 30.8% vs. phase III, 12.9%; p < 0.05), and rate of hemoptysis (phase I, 15.4% vs. phase III, 2.9%; p < 0.05). CONCLUSIONS: Thirteen cases were accumulated to lay the technical foundation, and 24 cases were required to achieve proficiency. In this study we summarize our own experience and provide specific guidance for young doctors with no experience in biopsy.

The disappearing hook wire: a case report.

Background: The migration of hook wire used for lung nodule localization to the pulmonary artery is an extremely rare complication. We report a case of migration of hook wire used for lung nodule localization to the main pulmonary artery and discuss the management. Case Description: The patient was a 50-year-old female with multiple pulmonary nodules, the largest of which was 7 mm and located in right lower lob. Since the size of the nodules were very small, three computed tomography (CT)-guided percutaneous hook wires were placed to localize the nodules prior to surgery. After entering the thorax, the wires were unable to be located in the right lower lobe and an intraoperative urgent chest CT demonstrated that the markers had migrated to the pulmonary artery. Therefore, the original surgical incision was extended and the superior tip subsegment of the pulmonary artery of the right lung was dissected open and the positioning needle was successfully removed. The patient was recovered without further complication and discharged 5 days later. Conclusions: When the exact location of a hook wire utilized for lung nodule localization cannot be determined, an exhaustive radiographic evaluation is required to determine the wire's specific location. If conditions permit, it is best to remove the hook wire directly using video-assisted thoracoscopic surgery (VATS). With careful perioperative assessment, surgeons can avoid additional complications and further surgery if they encounter a migrated nodule localization wire.

An Approach for Predicting the Low-Cycle-Fatigue Crack Initiation Life of Ultrafine-Grained Aluminum Alloy Considering Inhomogeneous Deformation and Microscale Multiaxial Strain.

In this paper, a low-cycle-fatigue (LCF) crack initiation life prediction approach that explicitly distinguishes nucleation and small crack propagation regimes is presented for ultrafine-grained (UFG) aluminum alloy by introducing two fatigue indicator parameters (FIPs) at the grain level. These two characterization parameters, the deformation inhomogeneity measured by the standard deviation of the dot product of normal stress and longitudinal strain and the microscale multiaxial strain considering the non-proportional cyclic additional hardening and mean strain effect, were proposed and respectively regarded as the driving forces for fatigue nucleation and small crack propagation. Then, the nucleation and small crack propagation lives were predicted by correlating these FIPs with statistical variables and cyclic J-integrals, respectively. By constructing a microstructure-based 3D polycrystalline finite element model with a free surface, a crystal plasticity finite element-based numerical simulation was carried out to quantify FIPs and clarify the role of crystallographic anisotropy in fatigue crack initiation. The numerical results reveal the following: (1) Nucleation is prone to occur on the surface of a material as a result of it having a higher inhomogeneous deformation than the interior of the material. (2) Compared with the experimental data, the LCF initiation life of UFG 6061 aluminum alloy could be predicted using the new parameters as FIPs. (3) The predicted results confirm the importance of considering the fatigue behavior of nucleation and small crack propagation with different deformation mechanisms for improving the fatigue crack initiation life prediction accuracy.

Caspase-1-mediated extracellular vesicles derived from pyroptotic alveolar macrophages promote inflammation in acute lung injury.

The occurrence and development of acute lung injury (ALI) involve a variety of pathological factors and complex mechanisms. How pulmonary cells communicate with each other and subsequently trigger an inflammatory cascade remains elusive. Extracellular vesicles (EVs) are a critical class of membrane-bound structures that have been widely investigated for their roles in pathophysiological processes, especially in immune responses and tumor progression. Most of the current knowledge of the functions of EVs is related to functions derived from viable cells (e.g., microvesicles and exosomes) or apoptotic cells (e.g., apoptotic bodies); however, there is limited understanding of the rapidly progressing inflammatory response in ALI. Herein, a comprehensive analysis of micron-sized EVs revealed a mass production of 1-5 µm pyroptotic bodies (PyrBDs) release in the early phase of ALI induced by lipopolysaccharide (LPS). Alveolar macrophages were the main source of PyrBDs in the early phase of ALI, and the formation and release of PyrBDs were dependent on caspase-1. Furthermore, PyrBDs promoted the activation of epithelial cells, induced vascular leakage and recruited neutrophils through delivery of damage-associated molecular patterns (DAMPs). Collectively, these findings suggest that PyrBDs are mainly released by macrophages in a caspase-1-dependent manner and serve as mediators of LPS-induced ALI.

[Experience of Thoracotomy and Robot-assisted Bronchial Sleeve Resection 
after Neoadjuvant Chemoimmunotherapy for Local Advanced Central Lung Cancer].

BACKGROUND: Immunoneoadjuvant therapy opens a new prospect for local advanced lung cancer. The aim of our study was to explore the safety and feasibility of robotic-assisted bronchial sleeve resection in patients with locally advanced non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. METHODS: Data of 13 patients with locally advanced NSCLC that underwent bronchial sleeve resection after neoadjuvant chemoimmunotherapy during August 2020 and February 2021 were retrospectively included. According to the surgical methods, patients were divided into thoracotomy bronchial sleeve resection (TBSR) group and robot-assisted bronchial sleeve resection (RABSR) group. Oncology, intraoperative, and postoperative data in the two groups were compared. RESULTS: The two groups of patients operated smoothly, the postoperative pathology confirmed that all the tumor lesions achieved R0 resection, and RABSR group no patient was transferred to thoracotomy during surgery. Partial remission (PR) rate and major pathological remissions (MPR) rate of patients in the TBSR group were 71.43% and 42.86%, respectively. Complete pathological response (pCR) was 28.57%. They were 66.67%, 50.00% and 33.33% in RABSR group, respectively. There were no significant differences in operative duration, number of lymph nodes dissected, intraoperative blood loss, postoperative drainage time and postoperative hospital stay between the two groups, but the bronchial anastomosis time of RABSR group was relatively short. Both groups of patients had a good prognosis. Successfully discharged from the hospital and post-operative 90-d mortality rate was 0. CONCLUSIONS: In patients with locally advanced central NSCLC after neoadjuvant chemoimmunotherapy can achieve the tumor reduction, tumor stage decline and increase the R0 resection rate, bronchial sleeve resection is safe and feasible. Under the premise of following the two principles of surgical safety and realizing the tumor R0 resection, robot-assisted bronchial sleeve resection can be preferred.

Surgical perspective in neoadjuvant chemoimmunotherapy for stage II-III non-small cell lung cancer.

BACKGROUND: There are many studies on neoadjuvant immunotherapy for locally advanced non-small cell lung cancer (NSCLC) patients. Expert consensus recommends neoadjuvant immunotherapy for patients with resectable stage IB-IIIA NSCLC. However, there are few clinical studies or cases to verify this. METHODS: Data were collected from all NSCLC patients who underwent surgical resection after neoadjuvant chemoimmunotherapy admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital between September 2020 and April 2021. Data collected included patient information, relevant examination results, intraoperative parameters, postoperative complications, pathological changes, and 90-day mortality. RESULTS: In total, 25 patients achieved R0 resection. Eleven (44%) patients completed surgery by thoracotomy, and three (12%) procedures were changed from minimally invasive procedures due to dense adhesions of hilar lymph nodes, which rendered it difficult to dissect the blood vessels. Thirteen (52%) patients achieved a major pathological response (MPR) with eight (32%) of these patients having a pathological complete response (pCR). Twenty-two (88%) patients showed radiological regression, and three (12%) patients had stable disease. The median drainage time was 8.50 (3-27) days. Thirteen (52%) postoperative complications were observed, but none were above grade 3. CONCLUSIONS: In this study, neoadjuvant chemoimmunotherapy was found to reduce tumor volume, cause pathological downstaging, and raise the surgical resection rate of patients with locally advanced NSCLC, and achieve a 100% R0 resection rate. There was an acceptable rate of postoperative complications. Thus, neoadjuvant chemoimmunotherapy is safe and practical.

Characterization of the heterogeneity of endothelial cells in bleomycin-induced lung fibrosis using single-cell RNA sequencing.

The loss of normal alveolar capillary and deregulated angiogenesis occurs simultaneously in idiopathic pulmonary fibrosis (IPF); however the contributions of specific endothelial subpopulations in the development of pulmonary fibrosis are poorly understood. Herein, we perform single-cell RNA sequencing to characterize the heterogeneity of endothelial cells (ECs) in bleomycin (BLM)-induced lung fibrosis in rats. One subpopulation, characterized by the expression of Nos3 and Cav1, is mostly distributed in non-fibrotic lungs and also highly expresses genes related to the "response to mechanical stimulus" and "lung/heart morphogenesis" processes. Another subpopulation of ECs expanded in BLM-treated lungs, characterized by Cxcl12, is observed to be closely related to the pro-fibrotic process in the transcriptome data, such as "regulation of angiogenesis," "collagen binding," and "chemokine activity," and spatially localized to BLM-induced neovascularization. Using CellPhoneDB software, we generated a complex cell-cell interaction network, which predicts the potential roles of EC subpopulations in recruiting monocytes, inducing the proliferation of fibroblasts and promoting the production and remolding of the extracellular matrix (ECM). Taken together, our data demonstrate the high degree of heterogeneity of ECs in fibrotic lung and it is proposed that the interaction between ECs, macrophages, and stromal cells contributes to pathologic IPF.

Clinical significance and functions of miR-203a-3p/AVL9 axis in human non-small-cell lung cancer.

Aim: We aimed to investigate the clinical significance and biological function of miR-203a-3p in non-small-cell lung cancer (NSCLC). Methods: The association between miR-203a-3p expression and clinicopathological parameters in NSCLC was assessed by χ2 test. Kaplan-Meier method and Cox regression model were applied to evaluate the prognosis value of miR-203a-3p. The biological function of miR-203-3p was explored using CCK-8 and transwell assays. Results: Significantly downregulated miR-203a-3p was associated with TNM stage, lymph node metastasis and poor prognosis. AVL9 was identified as a direct target of miR-203a-3p. Functionally, we found overexpression of miR-203a-3p inhibited cell proliferation, migration and invasion in NSCLC cells by targeting AVL9. Conclusion: Collectively, targeting the miR-203a-3p/AVL9 axis might help to develop useful therapeutic target for NSCLC.

A pilot study on clinicopathological features and intestinal microflora changes in colorectal cancer patients born over a nine-year period encompassing three years before and after the Great Chinese famine.

BACKGROUND: Exposure to energy restriction during childhood is associated with a lower risk of developing colorectal cancer (CRC). To date, the association between this critical period of growth and prognosis of CRC has rarely been investigated. Changes in microbiota and epigenetic dysregulation may be key underlying mechanisms. METHODOLOGY: Tissues collected from patients born between 1956 and 1964 were grouped based on time-period. The differences in overall survival among patients from the three time-periods were examined via univariate analysis. The 16S rRNA gene sequencing approach was to determine differences in microbiota among the groups. Samples were randomly selected to detect BRAF mutations, microsatellite instability (MSI) and promoter CpG island methylator phenotype (CIMP) status. The chi-square test was to assess the relationship between alterations in these molecules and microbiota differences. RESULTS: Patients from the three groups differed in terms of location of CRC (P = 0.034) and carcinoembryonic antigen (CEA) level (P = 0.036). A survival advantage was observed in the famine group compared with the other two groups. Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were more abundant in the two comparing groups. Abundance of B. fragilis was associated with BRAF mutations, microsatellite instability (MSI) and abundance of E. coli. Moreover, the incidence of CIMP and MSI was higher in patients with greater abundance of F. nucleatum. CONCLUSIONS: Limitation of energy intake during childhood may affect the composition of gut microbiota, resulting in persistent epigenetic changes that subsequently influence the prognosis of patients with CRC.

Silicon Nanowire/Polymer Hybrid Solar Cell-Supercapacitor: A Self-Charging Power Unit with a Total Efficiency of 10.5.

An integrated self-charging power unit, combining a hybrid silicon nanowire/polymer heterojunction solar cell with a polypyrrole-based supercapacitor, has been demonstrated to simultaneously harvest solar energy and store it. By efficiency enhancement of the hybrid nanowire solar cells and a dual-functional titanium film serving as conjunct electrode of the solar cell and supercapacitor, the integrated system is able to yield a total photoelectric conversion to storage efficiency of 10.5%, which is the record value in all the integrated solar energy conversion and storage system. This system may not only serve as a buffer that diminishes the solar power fluctuations from light intensity, but also pave its way toward cost-effective high efficiency self-charging power unit. Finally, an integrated device based on ultrathin Si substrate is demonstrated to expand its feasibility and potential application in flexible energy conversion and storage devices.

Foxo3a inhibits mitochondrial fission and protects against doxorubicin-induced cardiotoxicity by suppressing MIEF2.

Doxorubicin (DOX) as a chemotherapeutic drug is widely used to treat a variety of human tumors. However, a major factor limiting its clinical use is its cardiotoxicity. The molecular components and detailed mechanisms regulating DOX-induced cardiotoxicity remain largely unidentified. Here we report that Foxo3a is downregulated in the cardiomyocyte and mouse heart in response to DOX treatment. Foxo3a attenuates DOX-induced mitochondrial fission and apoptosis in cardiomyocytes. Cardiac specific Foxo3a transgenic mice show reduced mitochondrial fission, apoptosis and cardiotoxicity upon DOX administration. Furthermore, Foxo3a directly targets mitochondrial dynamics protein of 49kDa (MIEF2) and suppresses its expression at transcriptional level. Knockdown of MIEF2 reduces DOX-induced mitochondrial fission and apoptosis in cardiomyocytes and in vivo. Also, knockdown of MIEF2 protects heart from DOX-induced cardiotoxicity. Our study identifies a novel pathway composed of Foxo3a and MIEF2 that mediates DOX cardiotoxicity. This discovery provides a promising therapeutic strategy for the treatment of cancer therapy and cardioprotection.

Evolutionary biologic changes of gut microbiota in an 'adenoma-carcinoma sequence' mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine.

The molecular biological mechanisms underlying the evolutionary biologic changes leading to carcinogenesis remain unclear. The main objective of our study was to explore the evolution of the microbiota community and molecules related with CRC in the dynamic transition from normal colon epithelium to premalignant adenoma with the aid of an 'adenoma-carcinoma sequence' mouse CRC model induced by DMH. We generated a modified mouse CRC model induced by DMH for DNA sequences, and characterized the molecular networks. Data from 454 pyrosequencing of the V3- V5 region of the 16S rDNA gene and immunohistochemical detection of APC, P53, K-RAS and BRAF genes were assessed with Principal coordinates, UniFrac, and Kruskal-Wallis rank sum test. The inflammatory group showed enrichment of Bacteroidetes and Porphyromonadaceae (P < 0.01). OTUs affiliated with Firmicutes were enriched in the hyperproliferative group (P < 0.01). Rikenellaceae and Ruminococcaceae showed an increasing trend during the CRC process while the opposite pattern was observed for Prevotellaceaeand Enterobacteriaceae. OTUs related to Alistipes finegoldii were significantly increased during CRC development, P53, K-RAS and BRAF, were gradually increased (P < 0.05). Conversely, expression of APC was decreased during the course of development of CRC. Our results demonstrate that the biological evolutionary shift of gut microbiota, characterized by a gradual decrease in 'driver' bacteria and an increase in DNA damage-causing bacteria, is accompanied by tumor development in the CRC model. The synergistic actions of microbiota dysbiosis and effects of bacterial metabolites on related molecular events are proposed to contribute to the progression of CRC tumorigenesis.