Publications by authors named "Yunchao Huang"

130 Publications

UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1.

Mol Cell 2021 Jun 3. Epub 2021 Jun 3.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address:

The transition of oxidized 5-methylcytosine (5mC) intermediates into the base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that fails to rescue Uhrf1 phenotype, is physically and functionally associated with BER complex. We show that UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1. This nonproteolytic action stimulates XRCC1's interaction with the ubiquitin binding domain-bearing RAD23B, leading to the incorporation of TDG into BER complex. Integrative epigenomic analysis in mouse embryonic stem cells reveals that Uhrf2-fostered TDG-RAD23B-BER complex is functionally linked to the completion of DNA demethylation at active promoters and that Uhrf2 ablation impedes DNA demethylation on latent enhancers that undergo poised-to-active transition during neuronal commitment. Together, these observations highlight an essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.
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http://dx.doi.org/10.1016/j.molcel.2021.05.022DOI Listing
June 2021

High-resolution metabolomic biomarkers for lung cancer diagnosis and prognosis.

Sci Rep 2021 Jun 3;11(1):11805. Epub 2021 Jun 3.

Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, 650118, Yunnan, China.

Lung cancer is the leading cause of human cancer mortality due to the lack of early diagnosis technology. The low-dose computed tomography scan (LDCT) is one of the main techniques to screen cancers. However, LDCT still has a risk of radiation exposure and it is not suitable for the general public. In this study, plasma metabolic profiles of lung cancer were performed using a comprehensive metabolomic method with different liquid chromatography methods coupled with a Q-Exactive high-resolution mass spectrometer. Metabolites with different polarities (amino acids, fatty acids, and acylcarnitines) can be detected and identified as differential metabolites of lung cancer in small volumes of plasma. Logistic regression models were further developed to identify cancer stages and types using those significant biomarkers. Using the Variable Importance in Projection (VIP) and the area under the curve (AUC) scores, we have successfully identified the top 5, 10, and 20 metabolites that can be used to differentiate lung cancer stages and types. The discrimination accuracy and AUC score can be as high as 0.829 and 0.869 using the five most significant metabolites. This study demonstrated that using 5 + metabolites (Palmitic acid, Heptadecanoic acid, 4-Oxoproline, Tridecanoic acid, Ornithine, and etc.) has the potential for early lung cancer screening. This finding is useful for transferring the diagnostic technology onto a point-of-care device for lung cancer diagnosis and prognosis.
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http://dx.doi.org/10.1038/s41598-021-91276-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175557PMC
June 2021

Blood Tumor Mutational Burden as a Predictive Biomarker in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).

Front Oncol 2021 14;11:640761. Epub 2021 May 14.

Yunnan Cancer Hospital and The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Center, Kunming, China.

This study was designed to investigate the impact of blood tumor mutational burden (bTMB) on advanced NSCLC in Southwest China. The relationship between the tTMB estimated by next-generation sequencing (NGS) and clinical outcome was retrospectively analyzed in tissue specimens from 21 patients with advanced NSCLC. Furthermore, the relationship between the bTMB estimated by NGS and clinical outcome was retrospectively assessed in blood specimens from 70 patients with advanced NSCLC. Finally, 13 advanced NSCLC patients were used to evaluate the utility of bTMB assessed by NGS in differentiating patients who would benefit from immunotherapy. In the tTMB group, tTMB ≥ 10 mutations/Mb was related to inferior progression-free survival (PFS) (hazard ratio [HR], 0.30; 95% CI, 0.08-1.17; log-rank = 0.03) and overall survival (OS) (HR, 0.30; 95% CI, 0.08-1.16; log-rank = 0.03). In the bTMB group, bTMB ≥ 6 mutations/Mb was associated with inferior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank < 0.01) and OS (HR, 0.31; 95% CI, 0.14-0.7; log-rank < 0.01). In the immunotherapy section, bTMB ≥ 6 mutations/Mb was related to superior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank < 0.01) and objective response rates (ORRs) (bTMB < 6: 14.2%; 95% CI, 0.03-1.19; bTMB ≥ 6: 83.3%; 95% CI, 0.91-37.08; = 0.02). These findings suggest that bTMB is a validated predictive biomarker for determining the clinical outcome of advanced NSCLC patients and may serve as a feasible predictor of the clinical benefit of immunotherapies (anti-PD-1 antibody) in the advanced NSCLC population in Yunnan Province.
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http://dx.doi.org/10.3389/fonc.2021.640761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160368PMC
May 2021

The concept of broad exposure facilitates uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection.

J Cardiothorac Surg 2021 May 21;16(1):138. Epub 2021 May 21.

Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province, China.

Background: Systematic lymph node dissection is an important part of radical resection for lung cancer. Insufficient incision of the mediastinal pleura results in a tapered or tunnel-like operation surface, which increases the difficulty of uniportal video-assisted thoracoscopic mediastinal lymph node dissection. The objective of this study was to report our concept of broad exposure and investigate the efficacy and safety of this concept in uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection.

Methods: We retrospectively analyzed the clinical data of the 204 non-small cell lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery for anatomical lobectomy and systematic lymph node dissection following the concept of broad exposure. SPSS 23.0 software was used for statistical analysis.

Results: All operations were completed under uniportal video-assisted thoracoscopic surgery following the concept of broad exposure. The median surgery time was 102 (range, 76-285) minutes and the median blood loss was 50 (range, 20-900) milliliters. The median chest tube duration time was 2 (range, 1-6) days, the median postoperative hospital duration time was 5 (range, 4-10) days. The median number of dissected lymph node stations and dissected lymph nodes were 8 (range,6-9) and 15(range,12-19), respectively. The median number of dissected mediastinal lymph nodes stations and dissected mediastinal lymph nodes were 5(range,3-6) and 11(range,10-15), respectively. The up-staging rate of N staging was 6.86%. The postoperative complication rate was 10.29% and there was no perioperative death.

Conclusions: According to our results, it's effective and safe to perform uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection following the concept of broad exposure. This new concept not only emphasizes sufficient exposure, but also focuses on protection of important tissues.
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http://dx.doi.org/10.1186/s13019-021-01519-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140417PMC
May 2021

EphA2: A promising therapeutic target in breast cancer.

J Genet Genomics 2021 Mar 29. Epub 2021 Mar 29.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China; Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China. Electronic address:

EphA2 (ephrin type-A receptor 2), a receptor tyrosine kinase, is overexpressed in human breast cancers often linked to poor patient prognosis. Accumulating evidence demonstrates that EphA2 plays important roles in several critical processes associated with malignant breast progression, such as proliferation, survival, migration, invasion, drug resistance, metastasis, and angiogenesis. As its inhibition through multiple approaches can inhibit the growth of breast cancer and restore drug sensitivity, EphA2 has become a promising therapeutic target for breast cancer treatment. Here, we summarize the expression, functions, mechanisms of action, and regulation of EphA2 in breast cancer. We also list the potential therapeutic strategies targeting EphA2. Furthermore, we discuss the future directions of studying EphA2 in breast cancer.
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http://dx.doi.org/10.1016/j.jgg.2021.02.011DOI Listing
March 2021

Unique Profile of Driver Gene Mutations in Patients With Non-Small-Cell Lung Cancer in Qujing City, Yunnan Province, Southwest China.

Front Oncol 2021 13;11:644895. Epub 2021 Apr 13.

Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China.

Objective: Qujing City, Yunnan Province, China, has a high incidence of lung cancer and related mortality. The etiology of NSCLC in Qujing area and distribution of associated molecular aberrations has not been fully elucidated. This study aimed to reveal the profile of driver gene mutations in patients with non-small-cell lung cancer (NSCLC) in Qujing and explore their relationships with clinicopathological characteristics.

Methods: In this study, the mutation profiles of NSCLC driver genes, including , and , were investigated in patients with NSCLC from Qujing and compared with those from other regions in Yunnan Province. The associations between molecular mutations and clinicopathological characteristics were further analyzed.

Results: A distinct profile of driver gene mutations was discovered in patients with NSCLC from Qujing. Interestingly, a higher proportion of compound mutations, including G719X + S768I (19.65% vs 3.38%, P < 0.0001) and G719X + L861Q (21.10% vs 2.82%, P < 0.0001), was observed in patients with NSCLC in Qujing compared with patients in non-Qujing area, besides significantly different distributions of (46.01% vs. 51.07%, = 0.0125), (3.17% vs. 6.97%, = 0.0012), (0.5% vs. 2.02%, = 0.0113), and (23.02% vs. 7.85%, < 0.0001). Further, compound mutations were more likely associated with the occupation of patients (living/working in rural areas, e.g., farmers). Moreover, G12C was the dominant subtype (51.11% vs 25.00%, = 0.0275) among patients with NSCLC having mutations in Qujing.

Conclusions: Patients with NSCLC in Qujing displayed a unique profile of driver gene mutations, especially a higher prevalence of compound mutations and dominant G12C subtype, in this study, indicating a peculiar etiology of NSCLC in Qujing. Therefore, a different paradigm of therapeutic strategy might need to be considered for patients with NSCLC in Qujing.
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http://dx.doi.org/10.3389/fonc.2021.644895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076749PMC
April 2021

TRPS1 drives heterochromatic origin refiring and cancer genome evolution.

Cell Rep 2021 Mar;34(10):108814

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address:

Exploitation of naturally occurring genetic mutations could empower the discovery of novel aspects of established cancer genes. We report here that TRPS1, a gene linked to the tricho-rhino-phalangeal syndrome (TRPS) and recently identified as a potential breast cancer driver, promotes breast carcinogenesis through regulating replication. Epigenomic decomposition of TRPS1 landscape reveals nearly half of H3K9me3-marked heterochromatic origins are occupied by TRPS1, where it encourages the chromatin loading of APC/C, resulting in uncontrolled origin refiring. TRPS1 binds to the genome through its atypical H3K9me3 reading via GATA and IKAROS domains, while TRPS-related mutations affect its chromatin binding, replication boosting, and tumorigenicity. Concordantly, overexpression of wild-type but not TRPS-associated mutants of TRPS1 is sufficient to drive cancer genome amplifications, which experience an extrachromosomal route and dynamically evolve to confer therapeutic resistance. Together, these results uncover a critical function of TRPS1 in driving heterochromatin origin firing and breast cancer genome evolution.
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http://dx.doi.org/10.1016/j.celrep.2021.108814DOI Listing
March 2021

The effects of TGF-β1 on staphylococcus epidermidis biofilm formation in a tree shrew biomaterial-centered infection model.

Ann Transl Med 2021 Jan;9(1):57

Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Yunnan Cancer Center, The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Kunming, China.

Background: Transforming growth factor-β1 (TGF-β1) has a wide range of biological functions. It antagonizes lymphocyte response, inhibits pro-inflammatory cytokines, and serves as a signal to turn off the immune response and inflammatory response. To study the correlation between TGF-β1 and T helper (Th)1/Th2 cytokine levels in tree shrews, and to explore the effects of different levels of TGF-β1 on central venous catheter (CVC)-centered Staphylococcus epidermidis biofilm formation in tree shrews.

Methods: Tree shrews were injected with different concentrations of TGF-β1, and venous blood was drawn after 48 h to measure the levels of Th1 and Th2 cytokines. A CVC was placed into the femoral vein, and TGF-β1 at different concentrations and PIA- (ATCC12228) and PIA+ (ATCC35984) standard strains of Staphylococcus epidermidis were injected into the tree shrews to establish a biomaterial-centered infection (BCI) model. After 72 h, the CVC was removed, and biofilm formation was detected using the API bacterial identification system, semi-quantitative biofilm formation assay, and scanning electron microscopy.

Results: In the groups treated with TGF-β1 at different concentrations, the levels of Th1 cytokines interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were lower than those of normal group, while the levels of Th2 cytokines IL-6, IL-4 and IL-10 were higher than those of normal group. In the TGF-β1 groups at different concentrations, the positive rate of Staphylococcus epidermidis ATCC35984 biofilm formation was higher than that in non-TGF-β1 group, while there was no significant difference in the positive rate of Staphylococcus epidermidis ATCC12228 biofilm formation compared with that of the non-TGF-β1 group.

Conclusions: TGF-β1 causes the imbalance of Th1/Th2 cytokines and Th1/Th2 shift in tree shrews, leading to Th1 cell-led decline in cellular immune function. TGF-β1 promotes PIA+ Staphylococcus epidermidis biofilm formation in the tree shrew BCI model, but it has no significant influence on PIA-Staphylococcus epidermidis biofilm formation on the surface of CVCs.
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http://dx.doi.org/10.21037/atm-20-4526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859740PMC
January 2021

Dysregulation of ferroptosis may involve in the development of non-small-cell lung cancer in Xuanwei area.

J Cell Mol Med 2021 Mar 2;25(6):2872-2884. Epub 2021 Feb 2.

Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Hospital, Kunming, China.

The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non-small-cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para-carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up-regulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.
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http://dx.doi.org/10.1111/jcmm.16318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957160PMC
March 2021

AFF4 facilitates melanoma cell progression by regulating c-Jun activity.

Exp Cell Res 2021 02 5;399(2):112445. Epub 2021 Jan 5.

Yunnan Key Laboratory of Lung Cancer Research, Kunming, China. Electronic address:

Melanoma is characterized by high mortality and poor prognosis due to metastasis. AFF4 (AF4/FMR2 family member 4), as a scaffold protein, is a component of the super elongation complex (SEC), and is involved in the progression of tumors, e.g., leukemia, head and neck squamous cell carcinoma (HNSCC). However, few studies on AFF4 have focused on melanoma. Here, AFF4 expression levels and clinicopathological features were evaluated in melanoma tissue samples. Then, we performed cell proliferation, migration and invasion assays in A375 and A2058 cells lines in vitro to evaluate the role of AFF4 in melanoma. The effects of AFF4 knockdown in vivo were characterized via a xenograft mouse model. Finally, the correlation between c-Jun and AFF4 protein levels in melanoma was analyzed by rescue assay and immunohistochemistry (IHC). We found that AFF4 expression was upregulated in melanoma tumor tissues and that AFF4 protein expression was also closely related to the prognosis of patients with cutaneous melanoma. Moreover, AFF4 could promote the invasion and migration of melanoma cells by mediating epithelial to mesenchymal transition (EMT). AFF4 might regulate c-Jun activity to promote the invasion and migration of melanoma cells. Importantly, c-Jun was regulated by the AFF4 promoted melanoma tumorigenesis in vivo. Taken together, AFF4 may be a novel oncogene that promotes melanoma progression through regulation of c-Jun activity.
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http://dx.doi.org/10.1016/j.yexcr.2020.112445DOI Listing
February 2021

Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial.

Lancet Respir Med 2021 03 18;9(3):305-314. Epub 2020 Dec 18.

Department of Thoracic Oncology, Fujian Cancer Hospital, Fuzhou, China.

Background: Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China.

Methods: We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18-70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4-6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT03134872 (follow-up is ongoing).

Findings: Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0-14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6-15·4] vs 8·3 months [6·0-9·7]; hazard ratio 0·60 [0·45-0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group.

Interpretation: The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1-positive population.

Funding: Jiangsu Hengrui Medicine.
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http://dx.doi.org/10.1016/S2213-2600(20)30365-9DOI Listing
March 2021

A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer.

Ther Adv Med Oncol 2020 24;12:1758835920965849. Epub 2020 Nov 24.

Division of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China.

Background: Carboxyamidotriazole (CAI), a calcium channel blocker, inhibits tumor cell proliferation, metastasis, and angiogenesis. This trial aimed to determine whether CAI combined with conventional chemotherapy could prolong progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients.

Methods: Patients were assigned into groups (3:1 ratio) to receive either chemotherapy + CAI or chemotherapy alone. Cisplatin (25 mg/m) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m) on days 1 and 8 of each 3-week cycle for four cycles. CAI was administered at 100 mg daily with concomitant chemotherapy; this treatment was continued after chemotherapy was ceased until serious toxicity or disease progression had occurred. PFS was the primary endpoint, and the secondary endpoints were objective response rate (ORR), disease control rate, overall survival (OS), and quality of life.

Results: In total, 495 patients were enrolled in the trial: 378 in the chemotherapy + CAI group and 117 in the chemotherapy + placebo group. PFS was significantly greater in the chemotherapy + CAI [median, 134 days; 95% confidence interval (CI) 127-139] than in the chemotherapy + placebo (median, 98 days; 95% CI: 88-125) group, with a hazard ratio of 0.690 (95% CI: 0.539-0.883;  = 0.003). There was no difference in the OS rates of both groups. The ORR was greater in the chemotherapy + CAI group than in the chemotherapy + placebo group (34.6% 25.0%,  = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) 64 (55.2%);  = 0.014].

Conclusion: CAI + platinum-based chemotherapy prolonged PFS and could be a useful therapeutic option to treat NSCLC.

Clinical Trial Registration: chinadrugtrials.org.cn identifier: CTR20160395.
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http://dx.doi.org/10.1177/1758835920965849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692340PMC
November 2020

Uniportal video-assisted thoracoscopic lung sparing tracheo-bronchial and carinal sleeve resections.

J Thorac Dis 2020 Oct;12(10):6198-6209

Thoracic Surgery Department, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.

Pathology arising from the intrathoracic portion of the trachea (distal trachea), the carina and the main bronchi is usually neoplastic and is mainly treated with surgery. Resection of the intrathoracic portion of the trachea, the carina and the main bronchi for neoplastic lesions does not necessitate lung resection and is traditionally being conducted via open surgery. Video-assisted thoracic surgery (VATS) is witnessing an exponential growth and is the treatment of choice for early-stage non-small cell lung cancer (NSCLC). The experience accumulated over the past two decades along with the introduction of reliable and ergonomic technology, has led to the expansion of its indications. In this article we provide a detailed description of lung sparing distal tracheal, carinal and main bronchi resection for primary neoplasms of the airway, without involvement of the lung, with the uniportal video-assisted technique. The chest is entered through the fourth intercostal space, mid-axillary line. Dissection of the paratracheal space anteriorly, the tracheoesophageal groove posteriorly and the subcarinal space and division of the azygos arch are essential to mobilize the distal trachea and carina. Lateral dissection should be avoided beyond the points of division of the airway, as it may hinder the blood supply to the anastomosis. Any tension to the anastomosis should be relieved by release maneuvers. Ventilation is achieved through an endobronchial catheter, inserted into the left main bronchus through which a high-frequency jet ventilation catheter can be also inserted through it. The rationale of applying a minimally invasive technique for the conduction of tracheal and carinal resections, is to exploit its advantages, namely less pain, earlier mobilization and lower morbidity. Uniportal video-assisted resections of the distal trachea, carina and the main bronchi, are safe when conducted by experienced surgical and anesthetic teams.
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http://dx.doi.org/10.21037/jtd.2020.04.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656374PMC
October 2020

The LINC01260 Functions as a Tumor Suppressor via the miR-562/CYLD/NF-κB Pathway in Non-Small Cell Lung Cancer.

Onco Targets Ther 2020 20;13:10707-10719. Epub 2020 Oct 20.

Department of Thoracic Surgery, Shengli Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, People's Republic of China.

Purpose: Recently, long noncoding RNAs (lncRNAs) have been identified as novel and potential therapeutic targets in various cancer types. Nonetheless, the levels and biological effects of lncRNAs in non-small cell lung cancer (NSCLC) remain largely unknown. In this study, we aimed to identify the effects of lncRNA-LINC01260 throughout the progression of NSCLC and explore the underlying mechanism.

Methods: Quantitative real-time PCR (qRT-PCR) and Western blot were performed to measure LINC01260, miR-562, and CYLD expression and protein levels. Luciferase reporter assay was employed to investigate the relationship between LINC01260 and miR-562, and miR-562 and CYLD, respectively. The viability and migration of cells were evaluated using CCK-8, colony formation, and transwell assays. The effects of LINC01260 were identified through tumorigenesis in vivo. ELISA was performed to detect the activity of NF-κB and p65 expression.

Results: In NSCLC tissues and cell lines, LINC01260 expression was downregulated, which corresponded to a lower survival rate of patients with NSCLC. Knockdown of LINC01260 accelerated the proliferation, colony formation, and migration of NSCLC cells. Moreover, downregulation of LINC01260 inhibited apoptosis of NSCLC cells by regulating the expression of Bcl-2 and Bax proteins in vitro. In vivo, the downregulation of LINC01260 promoted tumor growth. miR-562 was identified as the target gene of LINC01260, which was upregulated in NSCLC tumors. Furthermore, CYLD was identified as the target gene of miR-562. The effects of LINC01260 were exerted by regulating CYLD via sponging miR-562. ELISA confirmed that the upregulation of CYLD inhibited NF-κB activity; however, the co-transfection of sh-LINC01260 partly reversed the inhibition. Additionally, CYLD reduced p65 expression; however, downregulation of LINC01260 slightly increased the expression level.

Conclusion: This study revealed a novel LINC01260/miR-562/CYLD/NF-κB pathway in the pathogenesis of NSCLC and suggested a potential therapeutic target for NSCLC.
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http://dx.doi.org/10.2147/OTT.S253730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585791PMC
October 2020

[Progress in Survival Prognosis of Segmentectomy for 
Early-stage Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2020 Sep;23(9):830-836

Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650105, China.

Surgery is currently the most appropriate treatment for early-stage non-small cell lung cancer (NSCLC). Increasing unilateral or bilateral multiple primary lung cancer being found, segmentectomy has attracted wide attention for its unique advantages in the treatment for such tumors. Ground glass opacity dominant early-stage NSCLC is associated with a good prognosis and can be cured by segmentectomy, however, the treatment of solid-dominant NSCLC remains controversial owing to the invasive nature. With the in-depth study on the lymph node metastasis pathway, radiological characteristics and molecular biology of NSCLC, a large part of solid nodules with certain characteristics can also be cured by segmentectomy. This paper reviews the research status and progress about the indication of segmentectomy.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.102.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519961PMC
September 2020

Research on the effect of TiO nanotubes coated by gallium nitrate on Staphylococcus aureus-Escherichia coli biofilm formation.

J Clin Lab Anal 2020 Sep 8;34(9):e23417. Epub 2020 Sep 8.

Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: In clinical practice, the cases with bacterial infection caused by titanium implants and bacterial biofilm formation on the surface of titanium materials implanted into human body can often be observed. Thus, this study aimed to demonstrate whether the mixed biofilm of Staphylococcus aureus/Escherichia coli can be formed on the surface of titanium material through in vitro experiments and its formation rules.

Methods: The titanium plates were put into the well containing S aureus or/and E coli. Bacterial adhesion and biofilm formation were analyzed by crystal violet, XTT method, confocal laser scanning microscopy, and scanning electron microscopy.

Results: The results of bacterial adhesion in each group at 6-72 hours showed that the number of bacterial adhesion in each group was increased with the extension of time and reached to the highest level at 72 hours. Moreover, the biofilm structure in the S aureus-E coli group was significantly more complex than that of the simple S aureus group or E coli group, and the number of bacteria was also significantly increased in the S aureus-E coli group.

Conclusion: Those data provide a laboratory basis for the prevention and treatment of mixed infection of subsequent biological materials.
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http://dx.doi.org/10.1002/jcla.23417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521225PMC
September 2020

[Cancer Screening Program in Urban Kunming of Yunnan: Evaluation of Lung Cancer Risk Assessment and Screening].

Zhongguo Fei Ai Za Zhi 2020 Jul;23(7):541-546

Department of Yunnan Cancer Center, Yunnan Cancer Center/Yunnan Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.

Background: Lung cancer is the most common neoplasmas with a poor prognosis and a low 5-year survival rate. Early screening is an important measure for the prevention and treatment of lung cancer. At present, different countries have issued corresponding lung cancer screening guidelines, but China still lacks guidelines based on Chinese population research. Therefore, the National Cancer Center launched a Multi-center Cancer Screening Program in Urban China. This study analyzed the evaluation of lung cancer risk assessment model and screening effect in urban China of Yunnan, so as to explore the evaluation model of high-risk lung cancer population suitable for China's national conditions and develop lung cancer screening guidelines for Chinese.

Methods: A questionnaire survey and lung cancer risk assessment were conducted on 165,337 people in 36 street offices in 4 main urban areas of Kunming, Yunnan Province, using cluster sampling method from January 2015 to December 2019. People with high-risk of lung cancer conducted low-dose computed tomography (LDCT) screening of chest. What's more, all participants were followed up by active or passive follow-up.

Results: There were 264 patients were diagnosed lung cancer by pathology, and the overall incidence of lung cancer was 0.16% (264/165,337). The high-risk group (0.31%, 116/37,914) was higher than the non-high-risk group (0.12%, 148/127,423), and the difference was statistically significant (P<0.001). The incidence of lung cancer in the high-risk group was higher than the non-high-risk group among the male, female, and lower 50-year-old or more than 50-year-old subgroups, with statistical differences (P<0.001), but there was no statistical difference in the group without LDCT screening (P=0.73). The sensitivity of the lung cancer high-risk population assessment model was 43.94% (116/264) and the specificity was 77.10% (127,275/165,073). The early diagnosis rate of the screening group was 72.97% (54/74), which was significantly higher than that of the non-screening group [28.48% (43/151)].

Conclusions: The lung cancer high-risk population assessment model of National Key Public Health Program: Cancer Screening Program in Urban China can detect high-risk populations and improve the early diagnosis rate of lung cancer effectively.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.101.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406440PMC
July 2020

Characterization of outdoor air pollution from solid fuel combustion in Xuanwei and Fuyuan, a rural region of China.

Sci Rep 2020 07 9;10(1):11335. Epub 2020 Jul 9.

Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rockville, MD, 20850, USA.

Outdoor air pollution is a growing public health concern, particularly in urban settings. However, there are limited epidemiological data on outdoor air pollution in rural areas with substantial levels of air pollution attributed to solid fuel burning for household cooking and heating. Xuanwei and Fuyuan are rural counties in China where the domestic combustion of locally sourced bituminous ("smoky") coal has been associated with the highest lung cancer rates in China. We previously assessed indoor and personal air pollution exposures in this area; however, the influence of indoor coal combustion and household ventilation on outdoor air pollution has not been assessed. Therefore, we measured outdoor fine particulate matter (PM), species of polycyclic aromatic hydrocarbons (PAHs) including naphthalene (NAP) and the known carcinogen benzo(a)pyrene (BaP), sulfur dioxide (SO), and nitrogen dioxide (NO) over two consecutive 24-h sampling periods in 29 villages. Just over half of the villages were revisited two to nine months after the initial sampling period to repeat all measurements. The overall geometric mean (GM) of outdoor PM, BaP, NAP, and NO were 45.3 µg/m, 9.7 ng/m, 707.7 ng/m, and 91.5 µg/m, respectively. Using linear mixed effects models, we found that burning smoky coal was associated with higher outdoor BaP concentrations [GM ratio (GMR) = 2.79] and lower outdoor SO detection rates (GMR = 0.43), compared to areas burning smokeless coal. Areas with predominantly ventilated stoves (> 50% of stoves) had higher outdoor BaP (GMR = 1.49) compared to areas with fewer ventilated stoves. These results show that outdoor air pollution in a rural region of China was associated with the type of coal used for cooking and heating indoors and the presence of stove ventilation. Our findings suggest that efforts of household stove improvement to reduce indoor air pollution have resulted in higher outdoor air pollution levels. Further reducing adverse health effects in rural villages from household coal combustion will require the use of cleaner fuel types.
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http://dx.doi.org/10.1038/s41598-020-68229-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347641PMC
July 2020

Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

J Cardiothorac Surg 2020 Jun 29;15(1):154. Epub 2020 Jun 29.

Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province, China.

Objective: It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype.

Methods: Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses.

Results: Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20-2.21) and OS (HR 1.53, 95% CI 1.19-1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45-2.85) and OS (HR 2.26, 95% CI 1.46-3.52) were also poor in the subgroup of patients with the presence of an MP component.

Conclusions: Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.
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http://dx.doi.org/10.1186/s13019-020-01199-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325156PMC
June 2020

A Phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer - The FALUCA study.

Lung Cancer 2020 08 20;146:252-262. Epub 2020 Jun 20.

The Fifth People's Hospital of Shanghai, China.

Objectives: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population.

Materials And Methods: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS).

Results: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires.

Conclusion: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.
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http://dx.doi.org/10.1016/j.lungcan.2020.06.016DOI Listing
August 2020

Two-Way: A Novel Method for Identifying the Anatomy During Uniportal Thoracoscopic Segmentectomy.

Ann Thorac Surg 2020 11 31;110(5):e441-e443. Epub 2020 May 31.

Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming, China.

Because the segmental bronchi and vessels are commonly variable and complicated, it is difficult to correctly identify them. Misidentification of the segmental anatomy could result in the failure of segmentectomy and conversion to other surgical procedures such as bisegmentectomy or lobectomy. We describe a novel method to identify the target segmental vessels and bronchi by exposing the adjacent segmental anatomy during uniportal video-assisted thoracoscopic segmentectomy, which could help to reduce the chance of misidentification.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.041DOI Listing
November 2020

miR-107 inhibited malignant biological behavior of non-small cell lung cancer cells by regulating the STK33/ERK signaling pathway and .

J Thorac Dis 2020 Apr;12(4):1540-1551

Department of Thoracic Surgery Ι, the Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Yunnan Cancer Center, The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Kunming 650118, China.

Background: The role of miRNAs in non-small cell lung cancer (NSCLC) has been broadly studied and confirmed, and miR-107 has attracted an ever-growing level of attention. This study set out to research the mechanism of the effect of miR-107 on the malignant biological behavior of NSCLC and .

Methods: The expression of miRNAs related to the development of NSCLC was detected by RT-qPCR. Western blotting was carried out to detect expression levels of serine/threonine kinase 33 (STK33) and proteins related to the extracellular regulated protein kinases (ERK) signaling pathway, while cell proliferation was detected using cell counting kit-8 (CCK-8). The cell apoptosis rate was measured using flow cytometry. The invasion ability was detected by Transwell assay. In vivo tumor growth assays were performed on mice. The expression ERK signaling pathway-related proteins was evaluated by immunohistochemistry staining. The targeted relationship between miR-107 and STK33 was confirmed by the dual luciferase reporter gene.

Results: In NSCLC cell lines and tissues, miR-107 was downregulated. Overexpression of miR-107 inhibited malignant biological behavior of NSCLC cell lines, and suppressed tumor growth . In addition, STK33 is one of the target genes of miR-107. Therefore, miR-107 suppressed cell proliferation and invasion and promoted tumor growth and cell apoptosis of NSCLC . The mechanism was found to be miR-107 targeting STK33, and a lack of STK33 led to the activation of ERK signaling pathway.

Conclusions: miR-107 inhibited malignant biological behavior of NSCLC through regulation of the STK33/ERK signaling pathway.
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http://dx.doi.org/10.21037/jtd.2020.03.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212150PMC
April 2020

Mechanistic study on the inhibition of biofilm by agrC-specific binding polypeptide.

Ann Transl Med 2020 Mar;8(6):337

Department of Thoracic Surgery I, the Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Yunnan Cancer Center, The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Kunming 650118, China.

Background: Considering the wide-spread misuse of antibiotics, the development of new antibacterial drugs may effectively prevent the emergence of antibiotic resistance in bacteria. The understanding of the mechanism underlying the agrC-specific binding polypeptide-mediated inhibition of biofilm formation may supply ideas for the development of new antibacterial drugs.

Methods: cells were cultured with different concentrations (0, 100, 200, 400, 800, and 1,600 µg/mL) of agrC-specific binding polypeptide (N1) and blank (N0). Crystal violet staining was performed to test the formation of biofilms and to determine the best concentration of agrC-specific binding polypeptides, and the bacterial inhibitory concentration was also determined. At different time points (6, 12, 18, 24, and 30 h), XTT assay was used to measure bacterial viability, and the real-time quantitative polymerase chain reaction was performed to measure the expression of , , , and genes. The sulfuric acid-phenol method was used to determine polysaccharide intercellular adhesin (PIA) levels.

Results: The biofilm formation ability of was the lowest after treatment with 800 µg/mL agrC-specific binding polypeptide. After 6 h of culture, agrC-specific binding polypeptide upregulated the expression of , , , and and increased the bacterial viability. However, the polypeptide downregulated the expression of , , , and and inhibited growth and PIA formation after 12 h of culture. Although agrC-specific binding polypeptide upregulated the expression of , , , and after 18 h, they inhibited bacterial growth and PIA formation.

Conclusions: Thus, agrC-specific binding polypeptide could downregulate the expression of , , , and and inhibit PIA formation by after 12 h, demonstrating its transient inhibitory effects on the biofilm formation ability of . Its effective concentration was 800 µg/mL.
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http://dx.doi.org/10.21037/atm.2020.02.84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186710PMC
March 2020

Identification of a potential tumor suppressor gene, , in non-small cell lung cancer.

Cancer Biol Med 2020 02;17(1):76-87

State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Oncogenes have been shown to be drivers of non-small cell lung cancer (NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to identify tumor suppressing ubiquitin pathway genes (UPGs) that were critical to lung tumorigenesis. The 696 UPGs were silenced by an siRNA screening in NSCLC cells; the potential tumor suppressing UPGs were analyzed, and their clinical significance was investigated. We reported that silencing of 11 UPGs resulted in enhanced proliferation of NSCLC cells, and four UPGs (, , , and ) were significantly downregulated in tumor samples compared to that in normal lung tissues and their expression levels were positively associated with overall survival (OS) of NSCLC patients. Among these genes, was the most significant one. expression was decreased in tumor samples compared to that in paired normal lung tissues in 59/86 (68.6%) NSCLCs, was correlated with TNM stage and sex of NSCLC patients, and was significantly higher in non-smoking patients than in smoking patients. Silencing UBL3 accelerated cell proliferation and ectopic expression of UBL3 suppressed NSCLC and . These results showed that UBL3 represented a tumor suppressor in NSCLC and may have potential for use in therapeutics and for the prediction of clinical outcome of patients.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142850PMC
February 2020

[Trend Analysis of Clinical Epidemiological Characteristics of Lung Cancer in Yunnan Cancer Hospital from 2005 to 2014].

Zhongguo Fei Ai Za Zhi 2020 Mar 27;23(3):142-149. Epub 2020 Feb 27.

Department of Yunnan Cancer Center, Yunnan Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Center, Kunming 650118, China.

Background: Yunnan is a country with a high incidence of lung cancer in China and all over the world, and its morbidity and mortality are still rising. With changes in lifestyle and environment, the clinical epidemiological characteristics of lung cancer are converting. However, the trend of clinical characteristics of lung cancer in Yunnan has not been reported in the past 10 years, and we should start further research. The aim of this study was to explore the clinical characteristics and changes of lung cancer in Yunnan from 2005 to 2014, and to provide a theoretical basis for lung cancer prevention and treatment in this region.

Methods: A retrospective survey was used to extract the cases of lung cancer patients who were treated in our hospital from 2005 to 2014 by simple random sampling. The sociodemographic and clinicopathological characteristics of the patients were extracted by using a unified and standardized questionnaire. And the statistical analysis of the data was performed.

Results: A total of 1,000 patients with lung cancer were enrolled, with an average age of (58.1±10.1) years, and the ratio of male to female was 3.08/1.00. The proportion of male patients decreased from 75.0% in 2005 to 66.0% in 2014, while female patients increased from 25.0% to 34.0% (P=0.007). The proportion of patients aged ≥60 years increased from 30.0% in 2005 to 39.0% in 2014, and the proportion of patients under 60 years of age decreased, but there was no statistical difference (P=0.532). The proportion of patients with lower levels of education (primary or junior high school) increased from 36.0% to 66.0% (P<0.001). The proportion of smokers decreased from 71.0% to 47.0%, and the number of non-smokers increased from 29.0% to 52.0% (P=0.003). The patients with advanced lung cancer (IIIb-IV) increased from 20.0% to 54.0%, while the proportion of stage II-IIIa decreased from 62.0% to 24.0% (P=0.002). The proportion of adenocarcinoma increased from 36.0% to 61.0%, while squamous cell carcinoma decreased from 32.0% to 27.0% (P<0.001). Chest X-ray applications decreased from 91.0% to 58.0% (P<0.001), while chest computed tomography (CT) usage increased from 46.0% to 89.0% (P<0.001). Head magnetic resonance imaging (MRI) usage increased from 1.0% to 15.0% (P<0.001). The bone scan increased from 35.0% to 78.0% (P<0.001). The positron emission tomography-CT (PET-CT) inspection technique increased significantly from 0.0% to 17.0%. Chemotherapy (P=0.67) and surgery (P=0.78) were the most common treatments and the treatments were unchanged over the past 10 years.

Conclusions: The proportion of female patients increased, the clinical stage was late, and the pathological type transformation was a major challenge in the prevention and treatment of lung cancer in Yunnan. Despite major changes in sociodemographic and clinicopathological features, the choice of primary treatment modalities has not changed, and further research is needed.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.03.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118330PMC
March 2020

International expert consensus on the management of bleeding during VATS lung surgery.

Ann Transl Med 2019 Dec;7(23):712

Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China.

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.
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http://dx.doi.org/10.21037/atm.2019.11.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989967PMC
December 2019

CYLD expression in dendritic cells involved in the immunoregulation of pulmonary adenocarcinoma via NF-κB pathway.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):137-142

Department of Thoracic Surgery, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou, China.

Our previous study found that IL33 repressed the growth of pulmonary adenocarcinoma (PA) via regulation of dendritic cells (DCs). However, the molecular mechanism of DCs in PA is still unclear. The present work showed that CYLD mice have a shorter survival rate of PA, and knockout CYLD in DCs also repress the progression of PA in mice. Subsequently, we found that decreased expression and reduced the nuclear translocation of NF-κB signalling was observed in CYLD knockout DCs, and inhibiting NF-κB pathway repressed DCs-induced proliferation and function of CD4 T cells. These results indicated that CYLD function as a tumour suppresser in PA regulates the function of DCs through NF-κB signalling pathway. Our findings support that CYLD serves as a potential target for immunotherapy in PA.
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http://dx.doi.org/10.1080/21691401.2019.1699820DOI Listing
December 2020

Study on the Effects of Estradiol in Staphylococcus epidermidis Device-Related Capsule Formation.

Aesthetic Plast Surg 2020 04 12;44(2):558-569. Epub 2019 Dec 12.

First Department of Mammary Surgery, Yunnan Cancer Hospital and The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan Province, China.

Background: Capsular contracture, mainly caused by Staphylococcus epidermidis (S. epidermidis) biofilm formation, is a complex problem for breast cancer patients who undergo surgical prosthetic breast reconstruction. Estradiol has been reported to be involved in the formation of bacterial biofilms. Thus, the underlying mechanism of estradiol in capsular contracture needs to be investigated.

Methods: Biofilm-related gene expressions were measured by qRT-PCR after sterilizing the silicone with bacterial suspension and E2 treatment in vitro. Rat models were established with bilateral ovariectomy operations and estradiol subcutaneous injections. The effects of estradiol on capsular contracture were detected by monitoring serum estradiol levels, bacterial infection rate in organs, biofilm formation and capsular contracture in vivo; inflammatory factors in vivo were examined as well. Biofilm on the silicone implants was observed under a scanning electron microscope.

Results: Both positive regulatory genes and negative regulatory genes were increased by the high concentration of estradiol, suggesting that estradiol can promote the formation of biofilm by not only positive but also negative regulations. High estradiol levels increased bacterial infection rate in organs, biofilm formation and capsular contracture. Further, high estradiol caused a large number of inflammatory cells to infiltrate and caused serious inflammatory reactions that aggravate the immune imbalances of the host.

Conclusion: High estradiol levels contribute to increasing capsular contracture caused by S. epidermidis biofilm formation.

No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-019-01567-3DOI Listing
April 2020