Objective: To explore the clinical effects of general anesthesia of sevoflurane inhalation in abdominal surgery for patients with mild-to-moderate chronic obstructive pulmonary disease (COPD). Methods: The clinical data of 68 patients with COPD abdominal surgery who admitted to the Department of Anesthesiology of Yiwu Central Hospital from June 2016 to June 2018 were retrospectively analyzed.According to the ratio of forced expiratory volume in 1 second in predicted value (FEV₁%pre), the patients were divided into mild group (FEV₁%pre≥80%, n=39) and moderate group (80%>FEV₁%pre≥50%, n=29). The blood gas indicators[arterial partial pressure of oxygen (PaO₂), arterial partial pressure of blood carbon dioxide (PaCO₂), blood oxygen saturation (SaO₂)], vital signs[heart rate (HR), mean arterial pressure (MAP)] and systemic vascular resistance (SVR) were compared between the two groups after entering (T0), after completion of induction (T1), at abdominal exploration (T2), before the end of surgery (T3) and after extubation (T4). The recovery quality indicators were analyzed in the two groups. Results: In the mild group at T1, T2 and T3, the PaO₂ values were (301.6±76.2)mmHg, (292.6±73.4)mmHg, (112.8±34.1)mmHg, respectively, and the SaO₂ values were (99.1±0.8)%, (98.8±1.0)%, (94.5±2.2)%, respectively, all of which were significantly improved compared with those at T0 (t=23.51, 22.73, 12.34, 2.75, 2.93, 2.22, all P<0.05), while the PaCO₂ values were (40.5±9.3)mmHg, (40.2±9.1)mmHg, (43.7±7.9)mmHg, respectively, which were significantly decreased compared with those at T0 (t=0.98, 1.12, 0.84, all P<0.05). The moderate group showed the same trend as the mild group, but there were no statistically significant differences between the two groups (all P>0.05). At T4, the PaO₂, PaCO₂ and SaO₂ levels in the two groups showed no significant changes compared with those at T0, and there was no statistically significant difference between the two groups at the same time (all P>0.05). At T1 and T2, the MAP levels in the mild group were (75.5±11.0)mmHg, (80.7±11.9)mmHg, respectively, the HR values were (71.4±12.5)times/min, (74.2±13.6)times/min, respectively, the SVR values were (9.1±1.6)×10² dynesos^-1ocm^-5, (9.9±2.0) ×10² dynesos^-1ocm^-5, which were significantly lower than those at T0 (t=1.35, 0.95, 1.83, 0.64, 1.42, 0.27, all P<0.05). The moderate group showed the same trend as the mild group, but there were no statistically significant differences between the two groups (all P>0.05). At T3 and T4, there were no significant changes in levels of MAP, HR and SVR between the two groups compared with those at T0, and there were no significant significant differences between the two groups (all P>0.05). The spontaneous breathing time, duration of eye opening, time of fist, time of removing tracheal catheter and time of returning to the ward in the mild group were slightly shorter than those in the moderate group (all P>0.05). Conclusion When general anesthesia of sevoflurane inhalation is used in abdominal surgery of COPD patients, the trend of blood gas indicators is not affected by COPD, which can provide reference for clinical establishment of anesthesia regimens.

Objective:This work aims to evaluate the clinical values of comprehensive genomic profiling examination based on circulating tumor DNA (ctDNA) in advanced lung cancer patients.Methods:This is a single-center, retrospective study that collected peripheral blood samples from patients with advanced lung cancer and performed gene mutation analysis using the TruSight Oncology 500 ctDNA assay kits. Between February 2022 and March 2023, a total of 82 patients were enrolled in Zhongshan Hospital, Fudan University, and 76 patients were included in the final analysis.According to the AMP/ASCO/CAP guidelines, mutations of targeted genes were divided into four levels (Tier I-IV), and the effectiveness of targeted therapy guided by ctDNA was evaluated. Descriptive statistics were used for basic characteristics, and the analysis of factors related to tumor mutational burden (TMB) was performed using the rank-sum test.Results:The ctDNA detection success rate was 92.7%(76/82).The median turnaround time for ctDNA testing was 10.5 days (9,13 days). At least one actionable mutation (Tier I or Ⅱ) was detected in 82.9%(63/76) of patients, and 28.6% (18/63) of patients received matched therapy, achieving a disease control rate of 18/18 and an objective response rate of 12/18.Conclusion:Comprehensive genomic profiling based on ctDNA can effectively identify actionable alterations in patients with advanced lung cancer and provide valuable information for matched therapy.

Objective:To verify the performance of the next-generation sequencing (NGS) platform and evaluate the application of NGS, droplet digital PCR (ddPCR) and super amplification refractory mutation system (super-ARMS) in the detection of circulating free DNA (cfDNA) mutations in patients with non-small-cell lung cancer (NSCLC).Methods:A total of 75 patients with NSCLC in the respiratory department of Zhongshan Hospital Affiliated to Fudan University were enrolled. The standards, cfDNA from 25 patients with newly diagnosed and untreated NSCLC, and self-made mixed samples mixed with hemoglobin (1 000 mg /dl), bilirubin (500 mg/l), fat emulsion (2%), enterococcus gDNA and Escherichia coli gDNA were used to verify the blank limit, analytical sensitivity, precision, accuracy and specificity of NGS platform. The cfDNA mutations of 75 NSCLC patients were detected by ddPCR and NGS, and the mutation positive rates of the two platforms were compared. The linear relationship between the two platforms was compared by Pearson correlation test. 12 patients were selected by simple random sampling for the detection of plasma super-ARMS platform. The performance of three platforms in the detection of plasma cfDNA mutation in patients with NSCLC was compared.Results:The blank limit of NGS platform was set to 0.00%, the analytical sensitivity was 0.2%, the intra-assay precision and inter-assay precision were 100%. The test results were not affected by endogenous hemoglobin, bilirubin or fat emulsion in plasma or exogenous DNA interference, and the analysis specificity was good. The mutation positive rates of plasma cfDNA in 75 NSCLC patients detected by ddPCR and NGS were 61.33% and 60.00%, respectively. The complete coincidence rate was 89.33%, which suggests there was a positive correlation between the mutation abundance of NGS and ddPCR ( r=0.984, P=0.001). Among the plasma of 12 NSCLC patients, the results of NGS, ddPCR and super-ARMS were completely consistent in 7 cases, including 2 wild-types and 5 mutants. Conclusion:The NGS platform was verified to be useful for cfDNA mutation detection in patients with NSCLC. The ddPCR, NGS and super-ARMS have their own advantages in detecting cfDNA mutations in patients with NSCLC.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*