Enhancing the Antitumor Efficacy of Oncolytic Adenovirus Through Sonodynamic Therapy-Augmented Virus Replication.

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.

Peptide-TLR7/8a-Coordinated DNA Vaccines Elicit Enhanced Immune Responses against Infectious Diseases.

DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(ß-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral ζ potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.

Cryo-Shocked Cancer Cells as an Oncolytic Adenovirus Reservoir for Glioblastoma Immunotherapy.

Glioblastoma is the most common type of primary brain tumor, which has a high recurrence rate and a high mortality rate. Immunotherapy shows promise in cancer therapy due to its capacity to manipulate the immune system to attack tumor cells with less toxic and durable immune responses. However, the low immunogenicity and limited immune cell infiltration in a glioblastoma lead to a weakened antitumor immune response, resulting in suboptimal therapeutic efficacy. A compelling solution is provided by oncolytic adenovirus (OAs), which can selectively replicate within tumor cells while simultaneously promoting antitumor immunity. Herein, we constructed an oncolytic adenovirus reservoir (OAR) by shocking OA-loaded tumor cells in liquid nitrogen to eliminate proliferation and pathogenicity. OARs showed sustained OAs release and effectively lysed tumor cells in vitro and in vivo. In a mouse intracranial glioblastoma model, OARs could efficiently induce dendritic cells' maturation, facilitate the tumor recruitment, and promote the infiltration of cytotoxic effector T lymphocytes via a single treatment, resulting in specific antitumor immune responses and long-term animal survival. Taken together, these results demonstrated that OAR is a promising synergistic therapeutic strategy for treating glioblastoma.

The effectiveness of web-based interventions on non-alcoholic fatty liver disease (NAFLD) in obese children: A study protocol for a randomized controlled trial.

Aim: Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease in the world, increasing the risk of cirrhosis and hepatocellular carcinoma, and contributing to the development of type 2 diabetes, cardiovascular disease, and chronic kidney disease. This study aims to carry out a web-based continuum of a care intervention model to provide comprehensive care interventions for obese children with NAFLD, to improve the effectiveness of treatment of children with NAFLD. Design: A 1-year single-blinded randomized clinical trial in hospital in Zhejiang Province. Methods: Eighty subjects will implement the program in a randomized order. The interventions for the control group mainly consisted of the routine distribution of health education materials and health education by holding health-themed lectures, and the preliminary proposed interventions including establishing management teams, regularly delivering related health knowledge, daily uploading of health intervention records, regular supervision and mutual encouragement, home visiting and psychological guidance. The primary outcomes are serum biomarkers such as alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), aspartate aminotransferase, and imaging (liver ultrasound and magnetic resonance imaging). Second outcomes are: BMI, waist-to-hip ratio and quality of life. In addition, socio-demographic characteristics such as age, gender and ethnicity will be recorded. Children aged 7-18 years old and diagnosed with NAFLD will be included, patients will be not eligible if they do not agree to participate or are participating in other health intervention programs. This study was registered on ClinicalTrials.gov (NCT05527938). Results: Over the past 30 years, NAFLD has been recognized as one of the most common liver diseases in adults and children. The current studies have focused on promoting lifestyle changes in children with NASH by providing some education and advice to children and their families to improve the histological features of NASH and lose weight. Because of the convenience and efficiency of the internet can provide some new strategies and ways for lifestyle interventions for children with NAFLD. In addition, we have designed a high-quality RCT based on the SPIRIT guidelines, which also provides strong evidence in this area.

Peptide-decorated nanocarriers penetrating the blood-brain barrier for imaging and therapy of brain diseases.

Blood-Brain Barrier (BBB) is one of the most important physiological barriers strictly restricting the substance exchange between blood and brain tissues. While the BBB protects the brain from infections and toxins and maintains brain homeostasis, it is also recognized as the main obstacle to the penetration of therapeutics and imaging agents into the brain. Due to high specificity and affinity, peptides are frequently exploited to decorate nanocarriers across the BBB for diagnosis and/or therapy purposes. However, there are still some challenges that restrict their clinical application, such as stability, safety and immunocompatibility. In this review, we summarize the biological and pathophysiological characteristics of the BBB, strategies across the BBB, and recent progress on peptide decorated nanocarriers for brain diseases diagnosis and therapy. The challenges and opportunities for their translation are also discussed.

Prevalence and associated factors for iron deficiency anemia among pregnant women in Fuyang, China.

Iron deficiency anemia (IDA) in pregnant women was associated with increased risks of both maternal and neonatal adverse outcomes. This study aimed to investigate the prevalence of IDA and identify the associated factors of IDA among pregnancy woman in Fuyang, China. The cross-sectional study was carried out in 789 pregnant women using simple random sampling method living in Fuyang, China from August 2017 to May 2018. Overall, the prevalence of IDA was 39.8%. 1-unit increment in maternal age was associated with a 5% increased risk of IDA, and 1-unit increased in BMI was associated with a 6% decreased risk of IDA (all P < .01). When compared with exercise for <30 minutes, 30-60 minutes of daily exercise was associated with a lower risk of IDA (P = .02). Similarly, when compared with a low frequency intake of iron-rich food, intake≥once/week was associated with a lower risk of IDA (P < .0001). However, vitamin C-rich food intake ≥twice/day was associated with a higher risk of IDA (P = .01) and a normal or bad appetite increased the risk of IDA when compared with a good appetite (P < .01). Our findings suggested that high frequency of iron-rich food intake, good appetite, and moderate physical activity were important for the prevention of IDA during pregnancy.

In Situ Oil Separation and Collection from Water under Surface Wave Condition.

Removal of oil from water is strongly desired due to environmental pollution, and related studies are mainly limited to the material itself. Here, we propose an oil-water separation device, called a floating well, which includes a container for oil collection and a modified mesh screen for oil separation. The mesh screen is superhydrophilic to oil and superhydrophobic to water. The oil removal experiment was performed in a basin. Under the calm surface condition, the oil collection efficiency is shown to be 42-69%. The inadequate oil collection is explained by the breakdown of a thin oil film above water to form an oil-free area, preventing direct contact between the separator and the oil. Sustained by a wave generator, we are surprised to find that with a low-frequency surface wave, the oil collection efficiency is increased to 98%, and the collection speed reaches 2.5 times that under the calm surface condition. The almost complete collection is due to the sustained contact between the separator and the oil, under which the surface wave continuously drives the oil film toward the separator from elsewhere, thus the oil-free area cannot be formed. Our work presents a new clue for large-scale in situ applications, in which the nature wave energy of river/sea can be the driving force for continuous oil separation and collection.

A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909).

BACKGROUND: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients. METHODS: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. DISCUSSION: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment. TRIAL REGISTRATION: NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.

Engineering extracellular vesicles for cancer therapy: recent advances and challenges in clinical translation.

Extracellular vesicles (EVs) are receiving increasing attention in recent years in the field of cancer treatment. EVs contain specific contents closely related to their donor cells, such as miRNAs, proteins and dsDNAs. As endogenous vesicles, EVs naturally have the characteristics of low toxicity and low immunogenicity and can stably pass through the circulatory system to reach the recipient cells, which make them good carriers to deliver therapeutic agents such as nucleic acid sequences and chemotherapeutics. In many preclinical studies and clinical trials, EVs have demonstrated their unlimited advantages in the field of cancer therapy. However, there are still some challenges that restrict their clinical application, such as yield, heterogeneity, safety, and specificity. In this review, we will focus on the latest breakthrough of EVs in the field of cancer treatment and discuss the challenges in the clinical translation of EVs.

Long-Term Outcomes of Treatments for Central Precocious Puberty or Early and Fast Puberty in Chinese Girls.

CONTEXT: Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking. OBJECTIVE: To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors. DESIGN AND SETTING: Retrospective, multicenter observational study from 1998 to 2017. PARTICIPANTS: Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n = 118), GnRHa alone (n = 276), or no treatment (n = 54). MAIN OUTCOME MEASURES: FAH, target height (Tht), and predictive adult height (PAH). RESULTS: The height gain (FAH-PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (P < 0.05; 9.51 ± 0.53, 8.07 ± 0.37, and 6.44 ± 0.91 cm, respectively). The genetic height gain (FAH-Tht) was 4.0 ± 0.5 cm for the GnRHa + rhGH group and 2.0 ± 0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, 5 critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH-PAH), and this was further validated using an independent study. CONCLUSIONS: The overall beneficial effect of GnRHa + rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication.

microRNA-301b-3p downregulation underlies a novel inhibitory role of long non-coding RNA MBNL1-AS1 in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the second most prevalent cause of cancer-related fatality. Long non-coding RNAs (lncRNAs) have been observed to exercise functions in NSCLC. Here, the current study aimed to explore the potential mechanism of lncRNA MBNL1-AS1 in NSCLC. METHODS: Microarray analysis was performed to screen the differentially expressed lncRNA associated with NSCLC and its potential mechanism. The lncRNA MBNL1-AS1 expression was quantified in 56 paired NSCLC and adjacent normal tissue samples. In an attempt to outline the function of lncRNA MBNL1-AS1 in NSCLC and to identify the interaction among lncRNA MBNL1-AS1, microRNA-301b-3p (miR-301b-3p) and TGFBR2, ectopic expression, depletion, and reporter assay experiments were conducted to detect CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. RESULTS: Initially, the intersection among lncRNA MBNL1-AS1, miR-301b-3p, and TGFBR2 was observed in NSCLC. While a poor expression of lncRNA MBNL1-AS1 and TGFBR2, along with a high expression of miR-301b-3p was observed in NSCLC tissues. A demonstration of lncRNA MBNL1-AS1 restoration significantly decreased CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 functioned as a sponge of miR-301b-3p, which inverted the inhibitory role of lncRNA MBNL1-AS1 in CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 positively regulated TGFBR2 which was a target gene of miR-301b-3p. At last, upregulated lncRNA MBNL1-AS1 or depleted miR-301b-3p suppressed the xenograft tumor formation in vivo. CONCLUSION: Collectively, the present study suggests an inhibitory role of lncRNA MBNL1-AS1 in CSC drug resistance of NSCLC by upregulating miR-301b-3p-targeted TGFBR2.

The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China.

BACKGROUND: To investigate the prevalence and risk factors of premature thelarche (PT) in girls and gynecomastia (GM) in boys in Southern China. METHODS: We conducted a cross-sectional study of preschool children across 9 cities in Zhejiang province. A total of 6273 children in the age-group of 2-7 years were recruited from January 2014 to March 2015. Relevant information was collected from mothers through face-to-face interviews. Logistic regression models were used to examine the correlates of PT and GM. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. RESULTS: The prevalence of PT among girls was 4.8% and that of GM among boys was 0.8%. One hundred girls were diagnosed with PT before the age of 2 years; 69 (69.0%) of these girls experienced spontaneous resolution of PT. Twenty-four boys were diagnosed with GM before the age of 2 years; 10 (41.7%) of these experienced spontaneous resolution of GM. Children borne of mothers with early onset of menarche and those belonging to high-income families were at a higher risk of premature breast development. Greater consumption of eggs was associated with premature breast development in early childhood. CONCLUSIONS: Socioeconomic status of family, early onset of menarche in mother, and consumption of eggs were strongly associated with premature breast development in early childhood.

The clinical significance of subcarinal lymph node dissection in the radical resection of oesophageal cancer.

OBJECTIVES: To explore the rule of subcarinal lymph node metastasis in thoracic oesophageal cancer and its clinical significance in the radical resection of oesophageal cancer. METHODS: We retrospectively analysed 2223 patients with oesophageal cancer who were admitted to Henan Cancer Hospital during 2004-2011 and underwent surgery as the first treatment option. Routine subcarinal lymph node dissections were performed, and the sections from the resected lymph nodes were embedded in paraffin for routine pathological examination. RESULTS: Subcarinal lymph node metastasis was observed in 200 patients (9%). Logistic regression analysis identified the following risk factors (P < 0.05): tumour location, depth of invasion into the oesophageal wall, tissue type, number of lymph node metastases, paraoesophageal lymph node metastasis (level 8 lymph nodes), left gastric cardiac lymph node metastasis. Unpaired t-test and χ(2)-test showed that more lymph node metastases, longer tumour length, deeper tumour invasion, middle oesophageal cancer, squamous-cell carcinoma, lower degree of differentiation, paraoesophageal lymph node metastasis and left gastric cardiac lymph node metastasis were associated with a higher frequency of subcarinal lymph node metastases (P < 0.05). Using the Kaplan-Meier method, recurrence and metastasis were shown to be more likely with solitary subcarinal lymph node metastasis than with solitary paraoesophageal lymph node metastasis (P = 0.001). CONCLUSIONS: Tumour location, depth of invasion, pathological type, degree of differentiation and other factors are closely associated with subcarinal lymph node metastasis. Recurrence and metastasis after oesophageal dissection are more likely with subcarinal lymph node metastasis.

Anterior mediastinal masses resection with cosmetic skin approach.

BACKGROUND: The objective of this study was to describe a cosmetic skin incision for resection of large anterior mediastinal masses, and to review our experience with this technique. METHODS: From 1999 to 2010, 55 patients with a diagnosis of large anterior mediastinal masses underwent "goblet"-shaped skin incision with midline sternotomy. The complications, mortality, details of surgery, and duration of hospital stay were observed from review. Patients were monitored via follow-up for a duration of one year after surgery. RESULTS: The mean hospital stay was nine days. Wound complications of infection were observed in one patient. There were no other complications, such as hematoma formation, necrosis of skin flap, split or infection of the sternum. No related mortality was recorded within the 30-day postoperative period. All of the patients verbalized the benefits of this technique, particularly the possibility of wearing open-collared clothing, as a result of the cosmetic chest wall and a camouflaging scar below the angle of Louis. At the follow-up periods, 52 of the patients were found to be well. Three patients did not complete follow-up at our facility. CONCLUSION: Our primary experience with this procedure proved it was safe. The technique allows excellent access to the mediastinum and complete removal of large anterior mediastinal masses that are complicated with adjacent midline cardiovascular structures. This technique also provides a better cosmetic result than the standard vertical incision.

[Surgical treatment of esophageal carcinoma with cervical esophagogastrostomy by left thoracic esophagectomy].

OBJECTIVE: To evaluate the effects of surgical treatment with cervical esophagogastrostomy by left thoracic esophagectomy on esophageal carcinoma. METHODS: The clinical data of 3169 patients with esophageal carcinoma, 2115 males and 1054 females, aged 60.9 (30-82), that underwent cervical esophagogastrostomy by left thoracic esophagectomy from Jan. 1990 to Dec. 2000 were analyzed retrospectively. RESULTS: The incidence of complication was 8.6% (273). The operative mortality was 0.6% (19). The 1, 3, and 5 year survival rates were 81.5%, 51.6%, and 32.1% respectively. Manometric examination of the digestive tract showed that the post-operative resting pressure of residual esophagus above the anastomotic stoma was (16+/-11 mm Hg), significantly higher than that of the cervical esophagus of the normal controls [(4+/-3) mm Hg), P<0.01]. CONCLUSION: Reducing incidence of gastroesophageal reflux and improving the quality of life of patients, cervical anastomosis should be recommended as the first choice procedure in treatment of upper and middle segment esophageal carcinoma.

[Blunt esophageal denudation without thoracotomy in the treatment of cervical esophageal carcinoma with laryngeal function preservation].

OBJECTIVE: To study the feasibility and effect of Blunt esophageal denudation without thoracotomy in the treatment of cervical esophageal carcinoma with laryngeal function preservation. METHODS: The data of 28 patients with cervical esophageal carcinoma, collected from Aug. 1997 to Nov. 2005, were investigated retrospectively. RESULTS: All the 28 patients were diagnosed as cervical esophageal squamous cell carcinoma. Among them, 12 patients underwent surgery (surgery group), while the other 16 patients underwent surgery plus radiation therapy preoperatively or postoperatively (multimodality therapy group). No uncontrolled intraoperative and postoperative hemorrhage and tracheal tear occurred. The incidence of complications was 21.4% (6/28), including cervical anastomotic leakage in 2 patients and recurrent laryngeal nerve injury in 4 patients. The overall 5-year survival rate was 50.3%. The 5-year survival rate was 25.7% in surgery group and 66.1% in multimodality therapy group, and the difference between two groups was statistically significant (chi(2)=4.07; P=0.0438). CONCLUSIONS: Blunt esophageal denudation without thoracotomy in the treatment of cervical esophageal carcinoma with larynx function preservation is possible. Combined with radiotherapy preoperatively or postoperatively, the survival time in patients with cervical esophageal carcinoma is able to be prolonged.

[Applications of polymerase chain reaction biochip/microdevice technology in the clinical diagnosis].

The polymerase chain reaction (PCR) technique has been widely used in fields of molecular biology and diagnosis. PCR biochip/microdevice is increasingly of great interest as a result of its small volume of sample and reaction mixture, short reaction period and portability. The applications of PCR biochip/microdevice are specially introduced in the clinical diagnosis. Finally, the applications and development of PCR biochip/microdevice are also predicted.

[Characteristics of lymph node metastasis in thoracic esophageal carcinoma].

OBJECTIVE: To investigate the frequency, distribution, and feature of lymph node metastasis in thoracic esophageal carcinoma, and to provide evidence for lymph node dissection and the multidisciplinary therapy for patients with esophageal carcinoma postoperatively. METHODS: The clinical data of 623 patients with thoracic esophageal carcinoma who had undergone esophagectomy plus lymph node dissection were studied to analyze the characteristics of lymph node metastasis. RESULTS: Totally 3689 of lymph node groups (with 8603 nodes) were dissected. The lymph node metastasis rate was 47.2% and lymph node metastasis ratio was 10.3%. No lymph node metastasis was found in the patients of Tis stage, while lymph node metastasis was found in the patients of other stages. There were significantly differences in lymph node metastasis rate and ratio among the patients of different T stages (chi2 = 38.407, P = 0.00, and chi2 = 118.438, P = 0.000). The higher the T stage, the higher the lymph node metastasis rate and ratio (r = 1, P = 0.000, and r = 1, P = 0.000). Different pathological types of esophageal carcinoma had different lymph node metastasis ratio (chi2 = 84.577, P = 0.000), however, there was no significant difference in lymph node metastasis rate among different pathological types (chi2 = 6.284, P = 0.179). The patients with squamous carcinoma had the lowest lymph node metastasis ratio and lymph node metastasis rate. The lymph node metastasis was mainly regional and extended vertically in both directions. Leaping over metastasis was another feature. All segments of thoracic esophageal carcinoma, especially lower thoracic esophageal carcinoma, could metastasize to the celiac lymph nodes. CONCLUSION: Lymph node dissection should be carried out properly in treatment of esophageal carcinoma and regional celiac lymph nodes should be explored and dissected more cautiously. Because surgical treatment is relatively radical in treatment of esophageal carcinoma, and taking the trend of lymph node metastasis and other indication into account, rational multidisciplinary therapy conducted as soon as possible should be adopted in the treatment of esophageal carcinoma.

[Proper operation mode of lung cancer: a clinicopathological study].

BACKGROUND: To investigate pathologically the characteristics of proximal bronchial invasion of lung cancer, and to provide the theoretic basis for the selection of a proper operation mode. METHODS: A total of 398 patients with lung carcinoma underwent radical pulmonectomy and systematic lymphadenectomy. The proximal bronchi and the hilar and mediastinal lymph nodes of their operatively resected specimens were selected for pathological study. RESULTS: (1)The direct invasion of cancerous cells through mucous, submucous or multiple layers was the most frequent way during lung cancer spread, rating 9.3%, 21.8% and 68.9% respectively. 96.4% of the cancerous invasion occurred at the proximal bronchial wall less than 1.5 cm apart from the cancer margin. The extension of invasion correlated with the histopathologic type of cancer, mode of invasion and TNM classification. (2)The cancer infiltration by the nodes metastasizing into the bronchus wall (bronchial external tunica or cartilage) was also an important way for the cancer to spread, especially in adenocarcinoma. The poor differentiated adenocarcinoma has significantly higher metastatic rate and infiltration rate than the well differentiated ( P < 0.01, P < 0.01). There were 22 such cases, including 3 of lobar bronchus wall invaded by N1 metastasis and 19 of main bronchus wall by N2 metastasis. CONCLUSIONS: For radical removal of tumor, the key point for selecting a rational operation mode is to keep a distance of 1.5 cm or more between the excision margin of the bronchus and the tumor, to pay attention to the bronchial wall invasion caused by the metastatic lymph nodes, even in peripheral adenocarcinoma, and to dissect extensively and completely the lymph nodes of the hilar and upper and lower mediastinum at the homolateral thoracic cavity.