Clinical significance of tumor mutation burden and DNA damage repair in advanced stage non-small cell lung cancer patients.

OBJECTIVE: This study aimed to investigate the impact of tumor mutational burden (TMB) and DNA damage repair (DDR) gene alteration on overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A DNA library of cancer cells from 67 NSCLC patients in stages III-IV was constructed for next-generation sequencing (NGS). Geneseeq422 probes were used for hybridization enrichment. The target-enriched library was sequenced on HiSeqNGS platforms, and we analyzed the relevant signaling pathways. Then, we correlated the OS of the patients with TMB and DDR mutations. RESULTS: Many significant alterations were found, including in the EGFR, p53, KRAS, RB1, ERBB2, NF1, DNMT3A, ALK, MYC, PIK3CA, ROS1, BRAF, ARID1A, PTEN, CDKN2A, and FGF19 genes. We also identified many mutations in the genes relevant to the DDR pathway. Interestingly, we found that the TMB of patients with DDR gene mutations was dramatically higher than that in the DDR wild-type (WT). Univariable analysis showed that DNMT3A, RB1, DDR pathway-related gene mutations, and TMB were critical factors for the effects on OS. Multivariable analysis confirmed that DNMT3A and mutations in the DDR pathway-related genes were important for predicting OS. CONCLUSIONS: Multiple mutations in the genes of the DDR pathway caused higher TMB levels, which resulted in longer OS. By contrast, OS was significantly longer in patients with non-DNMT3A mutations than in those with DNMT3A variants. DNMT3A alteration in NSCLC patients led to poor outcomes.

[Clinical study of butterfly cartilage myringoplasty for anterior quadrant tympanic perforation under endoscope].

Objective: To evaluate the results of butterfly cartilage myringoplasty for anterior quadrant tympanic perforation under endoscope. Methods: Thirty-eight patients with anterior quadrant tympanic perforations who were subjected to endoscopic butterfly cartilage myringoplasty from April 2016 to October 2018 were included in this study, including 16 males and 22 females, with an average age of (34.5±14.2) years. The patients were reviewed retrospectively, and the pre-and post-operative pure tone audiometry (PTA) thresholds, pre-and post-operative air-bone gaps (ABG), post-operative graft success rates and complications were evaluated. SPSS 23.0 was used to analyze data. Results: Mean post-operative follow-up duration was (9.4±3.1) months (range 6-18 months). The graft survival rate was 94.7% (36/38) . The preoperative and postoperative mean PTA was (30.9±8.9) dB HL and (21.4±7.7) dB HL respectively. Preoperative and postoperative mean ABG was (18.4±6.3) dB and (10.8±6.0) dB respectively. There was significant difference between pre-and postoperative PTA and ABG (t=5.353 and 4.162, P<0.05 for both). A postoperative ABG reduction of (8.3±1.5) dB was reached. Two (4.7%) patients had postoperative myringitis, two (4.7%) had recurrent perforation, and one (2.4%) had lateral healing of transplanted tympanic membrane in the postoperative follow-ups. No intratympanic cholesteatoma was observed. Conclusions: Endoscopic butterfly inlay myringoplasty is a reliable, minimally invasive alternative method to repair anterior tympanic membrane perforations, with high closure rate and low risk of complications.

[Clinical application of a self-developed bone dust collector in mastoid cavity obliteration following mastoidectomy].

Objective: To introduce a self-developed bone dust collector designed by the authors and evaluate its efficiency in mastoid obliteration following mastoidectomy. Methods: Consecutive patients, from April 2017 to March 2018, who prepared to receive mastoidectomy were randomly divided into two groups, and in each group the bone dust was harvested by self-developed bone dust collector or by conventional used method respectively in mastoidectomy. The amount of the harvested bone dust and the time consumed in the collecting procedure were compared between two groups. The infection of the bone dust after mastoid obliteration was also evaluated during follow up. Results: 33 patients were recruited in bone dust collector group, and 31 patients in conventional method group.There is no significance of difference between two groups in sex ratio, age and pneumatization of mastoid cells (P>0.05 for all). The median amount of bone dust harvested by bone dust collector was significantly larger than that collected by conventional method (1.8 g vs 1.1 g, P<0.05). The median time spent in bone dust collector group was significantly shorter than that spent in conventional method group (4 minutes vs 6 minutes, P<0.05). No bone dust infection was found in the follow-up in all patients. Conclusion: The present self-developed bone dust collector is a easy and useful apparatus which can significantly improve the efficiency of collecting bone dust in mastoidectomy.

ApoG2 as the most potent gossypol derivatives inhibits cell growth and induces apoptosis on gastric cancer cells.

Gastric cancer is one of the most common types of malignancies and proteins from the Bcl-2 family are highly expressed in human gastric cancer. Apogossypolone (ApoG2), the most potent gossypol derivative, has been defined as a novel small-molecule inhibitor of anti-apoptotic Bcl-2 family proteins. However, whether or not it can inhibit the growth and proliferation of gastric cancer cell lines has not been demonstrated to date. Here, we assessed the effects of anti-growth of ApoG2 on gastric cancer cell lines in vitro and explored the possible molecular mechanisms of ApoG2. Using the MTT assay and flow cytometry, we found that ApoG2 has the significant anti-growth effect on MKN28, MKN45 and AGS cell lines in a time- and dose-dependent manner. Compared to (-)-gossypol, MTT assay and flow cytometry results showed that anti-growth effect of ApoG2 is inferior, but the colony formation ability of ApoG2 is superior. Furthermore, western blot results revealed that ApoG2 inhibits the growth and proliferation of gastric cancer cells by down-regulating of Bcl-2 protein expression, up-regulating of Bax and activating of Caspase-3. Taken together, albeit the ApoG2 inferior to (-)-gossypol in many ways on gastric cancer in vitro, our results suggest that ApoG2 could effectively inhibit the growth and proliferation of gastric cancer cell lines through the mitochondrial pathway of apoptosis.

In vivo tumor detection on rabbit with biopsy needle as MRE driver.

Magnetic Resonance Elastography (MRE) is a phase contrast imaging technique to quantitatively measure the elasticity of tissues. Typically, the oscillating driver is placed on the surface of objects to generate shear waves. When it is applied to detect tumors in deep location, the depth penetration of the wave is limited by attenuation and the biopsy procedure has to be performed separately. In this study, we describe a method using biopsy needle as the MRE driver to produce shear waves in tissues. We made comparison between the MRE acquisitions obtained with biopsy needle and surface drivers. Because the well-defined propagation wave pattern reduces the error in wavelength calculation, the acquisitions of biopsy needle driver shows better homogeneity in stiffness map. We also performed the experiment with the biopsy needle for in vivo tumor detection in rabbits. This study demonstrates that the biopsy needle driver is more effective than the surface driver for accurately measuring the stiffness and location of the tumor.

Model for gas-laser interaction: application to thermally activated laser-induced chemical vapor deposition.

We present a model for the interaction between a laser and gas mixture that can be directly applied to the case of thermally activated laser-induced chemical vapor deposition (LICVD). The model involves the values of specific parameters, particularly gas pressure, laser intensity, detuning frequency, and rotational and vibrational relaxation rates, relevant to absorption, saturation, and heat-transfer processes and their interrelation. We adopt a semiclassical phenomenological approach, considering vibrational energy levels with accompanying rotational energy manifolds and both radiative and nonradiative transition processes. The model is applied to the experimental NH(3) absorption results at the R(6), R(14), and P(20) lines of a cw CO(2) laser in the 10-microm region.