[Reliability and validity of the Chinese version of the test of the adherence to inhalers (TAI)].

Objectives: To evaluate the reliability and validity of the Chinese version of the test of the adherence to inhalers (TAI) in Chinese patients with chronic airway disease. Methods: Based on the English version of TAI, the items of the Chinese version of TAI were determined after forward-backward translation and cultural adaption. Totally, 165 patients with chronic obstructive pulmonary disease (COPD) and asthma were enrolled from Respiratory Clinic of the Second Xiangya Hospital of Central South University from July to November 2021, and a questionnaire survey was conducted using the Chinese version of TAI and the Morisky medication adherence scale 8-item version (MMAS-8). The content validity of the scale was expressed by content validity index (CVI) and the construct validity was analyzed by exploratory factor analysis (EFA). The convergence validity was evaluated by Pearson correlation analysis. The reliability of the scale was expressed by Cronbach's α coefficient, the split-half reliability and test-retest reliability. Results: The CVI was 0.966. There were 10 items in total. Two factors were extracted from the Chinese version of TAI and the cumulative variance contribution rate was 57.236%. The load value of each item was more than 0.400 and the factor attribution of the item was consistent with the original scale. The total score of the Chinese version of TAI was positively correlated with the total score of the MMAS-8(r=0.835,P<0.001). The Cronbach's α of the overall scale was 0.843, the Guttman's half-reliability coefficient was 0.796 and the test-retest reliability was 0.884 (P<0.001), respectively. Conclusions: The Chinese version of TAI has good reliability and validity, which may be a reliable tool for evaluating the adherence to inhalers of patients with chronic airway disease in China.

[Effect of FBXW7 gene mutation on the prognosis of immunotherapy in patients with non-small cell lung cancer].

Objective: To explore the effect of F-box and WD-40 domain protein 7 (FBXW7) gene mutation on the prognosis of immunotherapy in patients with non-small cell lung cancer (NSCLC). Methods: (1) The clinical data of 125 patients with advanced NSCLC in the First Affiliated Hospital of Nanjing Medical University from January 2019 to June 2021 were collected. There were 70 males and 55 females, with a median age [M (Q1, Q3)] of 64(57, 70) years. The correlation of FBXW7 mutation with immunotherapy efficacy and prognosis was analyzed. (2) The Data set of NSCLC patients treated with immunotherapy from cBioPortal database was downloaded. A total of 261 patients were included as immunotherapy group. There were 120 males and 141 females, with a median age of 66(57, 73) years. The association of FBXW7 mutation with clinical characteristics and prognosis of NSCLC patients was investigated. (3) The data of patients with NSCLC from the cancer genome atlas (TCGA) database were downloaded. A total of 1 030 patients were included as TCGA group. There were 633 males and 397 females, with a median age of 67(60, 73) years. The effect of FBXW7 mutation on the efficacy of immunotherapy was analyzed. The key molecules and their biological functions were also determined Results: Among the 125 NSCLC patients, the FBXW7 mutation rate was 5.6% (7/125). All FBXW7 mutation types was truncating mutation. In these FBXW7 mutation patients who received immunotherapy, 4 had partial response, 2 had stable disease, and 1 had progressive disease. The objective response rate (ORR) and disease control rate (DCR) were 4/7 and 6/7, respectively. The median progression-free survival (PFS) was 13.0 months (95%CI: 7.0-22.0 months) for patients with FBXW7 mutation and 4.0 months (95%CI: 2.0-11.5 months) for patients with FBXW7 wild type, with a statistically significant difference (P=0.046). The bioinformatics analysis indicated that patients with FBXW7 mutation have higher clinical benefits from immunotherapy. Moreover, patients with FBXW7 mutation in immunotherapy group had higher tumor mutational burden (TMB) [M (Q1, Q3): 17.8 (11.5, 29.3)/Mb] than those with FBXW7 wild type [5.7 (3.0, 10.4)/Mb, P=0.001]. The TMB of patients with FBXW7 mutation in TCGA group was 15.9 (4.2, 28.1)/Mb, insertion-deletion (Indel) neoantigen was 192.5 (70.8, 535.0) and single nucleotide variant (SNV) neoantigen was 363.0 (194.8, 534.8), which were significantly higher than those of patients with FBXW7 wild type [5.6 (3.2, 8.9)/Mb, 53.0 (12.0, 131.0), 83.5 (34.0, 178.0), respectively] (P=0.002, P=0.008, P<0.001). The results indicated that FBXW7 mutated tumors had stronger immunogenicity, which might generate anti-tumor immunity. FBXW7 mutation was also related to the activation of T cells (T lymphocyte receptor complexes and signaling). In addition, FBXW7 mutation was correlated with increased infiltration of CD8+T cells and M1 macrophages. CD8+T cells and M1 macrophages infiltration level was significantly up-regulated in FBXW7 mutation group than wild-type group [10% (8%, 14%) vs 7%(4%, 12%), P=0.049; 8%(4%, 11%) vs 4%(1%, 8%), P=0.046]. Conclusions: NSCLC patients with FBXW7 mutant have higher clinical benefits from immunotherapy. FBXW7 mutation has the potential as a predictive marker for the efficacy of immunotherapy in NSCLC patients.

[Application and prospect of multiomics techniques in susceptibility to occupational noise hearing loss].

With the continuous innovation of technology, genomics and other omics techniques, such as transcriptomics, proteomics, and metabolomics, are increasingly becoming an important basis for precision medicine. Current research on susceptibility to occupational noise hearing loss (ONHL) has focused on genomics. Building the future of precision medicine is the focus of current ONHL research. Compared to single-omics studies, the use of multi-omics analysis can provide an integrated flow of information on ONHL susceptibility. This paper outlines the advantages and limitations of different histological techniques and the application of each histology in the disease, and focuses on the feasibility of applying multi-omics techniques in ONHL susceptibility research. The analysis of multi-omics techniques can better guide the comprehensive understanding of the disease in clinical research.

[Effect of serum lipid level on prognosis of patients with small cell lung cancer at the initial treatment].

Objective: To investigate the effect of serum lipid level on prognosis of patients with small cell lung cancer (SCLC) at the initial treatment. Methods: The clinical data of patients with SCLC from 2012 to 2017 in our hospital were retrospectively analyzed. According to the standard of appropriate level and abnormal stratification of blood lipid in Chinese population, the lipids included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) at the time of initial treatment were grouped. Then the relationship between different lipid levels and clinicopathological characteristics was analyzed. Finally, Cox proportional hazard model was used to analyze the independent prognostic factors of patients. Results: A total of 129 patients with SCLC were included in this study. At the time of initial treatment, there were 90 (69.8%) cases whose TC < 5.2 mmol/L, while 39 (30.2%) cases ≥5.2 mmol/L; 95 (73.6%) cases whose TG <1.7 mmol/L, while 34 (26.4%) cases ≥1.7 mmol/L; 27 (20.9%) cases whose HDLC <1.0 mmol/L while 102 cases (79.1%) ≥1.0 mmol/L; 90 (69.8%) cases whose LDLC <3.4 mmol/L while 39 cases (30.2%) ≥3.4 mmol/L. The patients' triglyceride initial treatment was associated with their body mass index (P<0.05). The median disease-free survival (PFS) of SCLC patients was related with their serum TC level and clinical stage (P<0.05) and the overall survival (OS) was related with clinical stage of SCLC patients (P<0.05). The median PFS of SCLC patients in the TC <1.7 mmol/L group at the initial treatment was 10.5 months, significantly longer than 8.8 months of the TC ≥1.7 mmol/L group (P=0.024). The median OS of SCLC patients in the TG <1.7 mmol/L group at the initial treatment was 20.2 months, marginally longer than 15.6 months of the TG ≥1.7 mmol/L group (P=0.097). Multivariate analysis result showed that, the TG level was an independent risk factor of SCLC progression at the time of initial treatment (P=0.024). There was no significant correlation of TC, HDLC, LDLC and SCLC prognosis (P>0.05). Conclusion: TG level is an independent risk factor for the progression of SCLC at the time of initial treatment, and the increase of TG level indicates rapid disease progression and poor prognosis.

[Spectrometric analyses of larotaxel and larotaxel liposomes quantification by high performance liquid chromatography].

OBJECTIVE: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes. METHODS: The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes. RESULTS: The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 µm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%. CONCLUSION: The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.

[Blood eosinophils: a biomarker of response to glucocorticoids and increased readmissions in severe hospitalized exacerbations of COPD].

Objective: To compare the clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) by different levels of blood eosinophil (EOS) count and to investigate the predictive value of the response to glucocorticoid treatment and the readmission rate in the patients with higher blood eosinophils. Methods: A total of 120 patients with AECOPD were admitted to the Department of Pulmonary and Critical Care Medicine in The Second Xiangya Hospital of Central South University from January 01, 2017 to December 31, 2017. Patients were divided into two groups according to their admission blood eosinophil fractions. Patients with EOS%≥2% were in the EOS group (n=56) , while patients with EOS%<2% were in the Non-EOS group (n=64) . The clinical characteristics, hospitalization treatments especially the glucocorticoid treatment response were compared, and the risk of severe acute exacerbation of the two groups including the 12-month COPD-related readmission, and time to first COPD-related readmission were also compared. Results: Compared with the Non-EOS group, the EOS group had lower values of white blood cell (WBC) , neutrophil fraction (N%) , blood neutrophil-to-lymphocyte ratio (NLR) , and C-reactive protein (CRP) . The EOS group also required shorter course of antibiotic treatment [8 (6-10) and 9 (7-11) , P=0.033]. In glucocorticoid-treated patients (n=82) , the EOS group had significantly alleviated symptoms than the Non-EOS group (patients withδCAT≥2 were 86.8% and 68.2%, respectively, P=0.046) , and the duration of hospitalization of the EOS group was shorter [9 (7-11) and 10 (9 to 13) , P=0.042]. Patients with glucocorticoid treatment in the EOS group had significantly alleviated symptoms than those without glucocorticoid treatment (patients with δCAT ≥ 2 were 86.8% and 61.1%, respectively, P=0.040) . The follow-up one year after discharge showed a higher risk of severe acute exacerbation in the EOS group [Adjust OR 2.67 (1.10-6.46), P=0.030; HR: 1.57 (1.02-2.40), P=0.040]. Conclusion: The blood eosinophil levels were useful in predicting the AECOPD patients' response to glucocorticoid treatment and the risk of severe acute exacerbations.

Growth retardation in senescent arterial smooth muscle cells and its reversal following brain stimulation: implications for atherogenesis.

Advancing age and psychosocial stress are each associated with a rising incidence of atherosclerosis. In this investigation we attempted to answer the question of whether they are independent of each other or not. Since a key feature of atherosclerosis is the proliferation of arterial smooth muscle cells (ASMC), we transplanted aortic tissue from aged rats, half of which had received hypothalamic stimulation, as a model for stress, to growth supporting medium, immediately after stimulation and observed their growth behavior for a period of 4 months. Similar observations were carried out on young animals for comparison. Although there was little difference in outgrowth frequency of explants from young animals between stimulated and non-stimulated subjects, in the case of the older rats, explants from animals which were not stimulated were considerably retarded in their growth, whereas those from subjects which had received HS, grew as well as those of the younger ones. These results show that HS can reverse the growth decline in aortic tissues explanted from senescent rats. They also suggest that age per se is not atherogenic in terms of proliferative behavior of ASMC, whereas when interacted with a stressful condition, this may be the case. Since in the elderly there is a decreased tolerance to stress, the 'atherogenic' effects of age in these individuals may be mediated through the stress response.

Age differences in the proliferative response of cultured arterial smooth muscle cells induced by sera of hypothalamically-stimulated rats.

In an earlier report, it was shown that arterial smooth muscle cells (ASMC) cultured from normal rat aorta, proliferated in response to homologous sera from young rats which had received hypothalamic stimulation (HS), in contrast to the effect of sera from non-stimulated age-matched controls (sham-operated). In the present study, this proliferative response was compared in young and old rats. Isolated target cells were subcultured from primary explants of aortic tissue obtained from young, male, Fischer 344 rats, which were electrode-implanted in the hypothalamus but not stimulated. After an initial quiescence period (growth arrest), target cells were exposed to plasma derived serum (PDS) from 4 experimental groups: young stimulated rats; young sham-operated controls; aged stimulated rats and aged sham-operated controls, at PDS concentrations of 2.5% and 5.0% and counted at days 2 and 5. Proliferative responses of ASMC were found to be influenced by concentration of the PDS, age of the donor animal contributing the serum and the presence of HS. The greatest responses were observed in relation to sera derived from aged stimulated rats, especially at the higher concentration, suggesting an interaction of HS with advanced age. These results are discussed in reference to their possible bearing on the pathogenesis of atherosclerosis.