The functional role of respiratory microbiota has attracted an accumulating attention recently. However, the role of respiratory microbiome in lung carcinogenesis is mostly unknown. Our study aimed to characterize and compare bilateral lower airway microbiome of lung cancer patients with unilateral lobar masses and control subjects. Protected bronchial specimen brushing samples were collected from 24 lung cancer patients with unilateral lobar masses (paired samples from cancerous site and the contralateral noncancerous site) and 18 healthy controls undergoing bronchoscopies and further analyzed by 16S rRNA amplicon sequencing. As results, significant decreases in microbial diversity were observed in patients with lung cancer in comparison to the controls, alpha diversity steadily declined from healthy site to noncancerous to cancerous site. Genus Streptococcus was significantly more abundant in cancer cases than the controls, while Staphylococcus was more abundant in the controls. The area under the curve of genus Streptococcus used to predict lung cancer was 0.693 (sensitivity = 87.5%, specificity = 55.6%). The abundance of genus Streptococcus and Neisseria displayed an increasing trend whereas Staphylococcus and Dialister gradually declined from healthy to noncancerous to cancerous site. Collectively, lung cancer-associated microbiota profile is distinct from that found in healthy controls, and the altered cancer-associated microbiota is not restricted to tumor tissue. The genus Streptococcus was abundant in lung cancer patients and exhibited moderate classification potential. The gradual microbiota profile shift from healthy site to noncancerous to paired cancerous site suggested a change of the microenvironment associated with the development of lung cancer.

BackgroundEarly-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening.MethodsIn this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited.ResultsAfter ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis.ConclusionES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

Intersphincteric resection is a safe procedure for sphincter-saving rectal surgery in selected patients with very low rectal tumors. A temporary diverting stoma may be beneficial to improve anal function. Modified partial intersphincteric resection under the precondition of radical resection yielded better anal function and a lower rate of incontinence.

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) positive dermatomyositis (DM) is a life-threatening disease often complicated with rapidly progressive interstitial lung disease (ILD). This study aimed to establish and validate a clinical prediction model for 6-month all-cause mortality in Chinese patients with anti-MDA5 positive DM-ILD. Methods We conducted a retrospective observational study using a single-centre derivation cohort and a multi-centre validation cohort. Hospitalized DM patients with positive anti-MDA5 antibody and ILD course ≤3 months on admission were included. Patients’ baseline characteristics were described and compared between the deceased and survivors by univariable Cox regression. Optimal cut-off values were defined by the ‘survminer’ R package for significant continuous variables. Independent prognostic factors were determined by the final multivariable Cox regression model chosen by backward stepwise algorithm, which could be reproduced in both cohorts. The Kaplan-Meier survival analyses based on the derived predictor were conducted. Results A total of 184 and 81 eligible patients were included with a cumulative 40.8% and 40.7% six-month mortality in the derivation and validation cohorts, respectively. Based on multivariable Cox regression, the prognostic factor at baseline was identified and validated as three-category forced vital capacity (FVC)%: FVC% ≥ 50%, FVC% <50%, unable to perform. This significantly distinguishes three risk stages with mortalities of 15.3%, 46.8%, 97.4% in the derivation cohort, and 14.9%, 58.3%, 86.4% in the validation cohort, respectively (all p < 0.05). Conclusion The validated FVC%-based categorical predictor in anti-MDA5 positive DM-ILD is helpful for risk stratification in clinical practice and might facilitate cohort enrichment for future trials.

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Ki-67 is a nuclear antigen widely used in routine pathologic analyses as a tumor cell proliferation marker for lung cancer. However, Ki-67 expression analyses using immunohistochemistry (IHC) are invasive and frequently influenced by tissue sampling quality. In this study, we assessed the feasibility of noninvasive magnetic resonance imaging (MRI) in predicting the Ki-67 labeling indices (LIs). A total of 51 lung cancer patients, including 42 non-small cell lung cancer (NSCLC) cases and nine small cell lung cancer (SCLC) cases, were enrolled in this study. Quantitative MRI parameters from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) were obtained, and their correlations with tumor tissue Ki-67 expression were analyzed. We found that the true diffusion coefficient (D value) from IVIM was negatively correlated with Ki-67 expression (Spearman r =-0.76, P < 0.001). The D values in the high Ki-67 group were significantly lower than those in the low Ki-67 group (0.90 ± 0.21 × 10-3 mm 2 /s vs. 1.22 ± 0.30 × 10-3 mm 2 /s). Among three MRI techniques used, D values from IVIM showed the best performance for distinguishing the high Ki-67 group from low Ki-67 group in receiver operating characteristic (ROC) analysis with an area under the ROC curve (AUROC) of 0.85 (95% CI: 0.73-0.97, P < 0.05). Moreover, D values performed well for differentiating SCLC from NSCLC with an AUROC of 0.82 (95% CI: 0.68-0.90), Youden index of 0.72, and F1 score of 0.81. In conclusion, D values were negatively correlated with Ki-67 expression in lung cancer tissues and can be used to distinguish high from low proliferation statuses, as well as SCLC from NSCLC.

Synaptotagmins are a class of proteins that play an important role in the secretion of neurotransmitters by synaptic vesicles. However, recent studies have shown that members of this family also have a certain function in the development of tumors. In this study, we first identified through The Cancer Genome Atlas data analyzed that a novel synaptotagmin, SYT13, was closely related to the prognosis of lung adenocarcinoma, but was not significantly correlated with the prognosis of lung squamous cell carcinoma. Then we knocked down the expression of SYT13 gene in lung adenocarcinoma cell lines A549 and H1299, and successfully induced decreased proliferation and clonality of lung adenocarcinoma cell lines, and observed cell cycle arrest and apoptosis enhancement in both cell lines. In addition, we detected the migration ability of SYT13 knockdown lung adenocarcinoma cell lines by the cell scratch test and the transwell test. Interestingly, there was a decreased migration ability of SYT13 knockdown in H1299 cells even though there was no significant difference in the migration of A549 cells. These results demonstrate that SYT13 plays an important role in the development of lung adenocarcinoma, which deepens our understanding of the mechanism of lung adenocarcinoma development and provides new possibilities for targeted therapy of lung adenocarcinoma.

PurposeTo compare conventional diffusion weighted imaging (DWI), intravoxel incoherent motion imaging (IVIM) and diffusion kurtosis imaging (DKI) in differentiating malignant and benign lung lesions.MethodFifty-five consecutive patients with lung lesions underwent multiple b-value DWI. The apparent diffusion coefficient (ADC), IVIM and DKI parameters were calculated using postprocessing software and compared between the malignant and benign groups. Receiver operating characteristic (ROC) analysis was performed for all parameters.ResultsADC and D were lower in malignant lesions than in benign lesions, while Kapp was higher (P &lt; 0.05). The differences in D*, f, and Dapp between the two groups were not significant (P &gt; 0.05). The areas under the curves (AUCs) of ADC, D, and Kapp were 0.816, 0.864, and 0.822. The combination of all the significant parameters yielded an AUC of 0.880. There were no significant differences in diagnostic efficacy among ADC, D, Kapp and the predictor factor (PRE).ConclusionsIn this study, traditional DWI (ADC), IVIM (D), and DKI (Kapp) all had good diagnostic performance in differentiating malignant lung lesions from benign lesions, but the combination of ADC, D, and Kapp value had better diagnostic efficacy than these parameters alone.