Fractional exhaled nitric oxide in checkpoint inhibitor pneumonitis: a case report and literature review.

Checkpoint inhibitor pneumonitis (CIP) is a relatively rare adverse event and a potential cause of death in patients treated with immune checkpoint inhibitors (ICIs). Because the symptoms and signs are nonspecific, the diagnosis of CIP is challenging. Additionally, compared with the biomarkers that can monitor the effect of ICIs, there is less research evaluating markers to monitor CIP. We report a case of CIP induced by camrelizumab in a patient with advanced non-small-cell lung cancer, in which the fractional exhaled nitric oxide levels showed obvious increases. Fractional exhaled nitric oxide may have the potential to monitor the condition of airway inflammation in patients using ICIs.

We report a patient with advanced lung cancer who experienced shortness of breath induced by immunotherapy. The levels of nitric oxide from the exhaled breath in this case showed obvious increases. Currently, monitoring systems for treatment-related lung injury remain elusive. This is the first report highlighting the potential value of measuring nitric oxide from the exhaled breath to screen for airway inflammation in patients receiving immunotherapy. The dynamic changes of the levels of nitric oxide from the exhaled breath may be correlated with the development of airway inflammation during immunotherapy.

MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia-Induced Myocardial Apoptosis.

Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.

Clinical characteristics of coronavirus disease 2019 in Gansu province, China.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has outbreak in the world. Little is known about the clinical characteristics of patients with SARS-CoV-2 infection in the high-altitude region of China. We reported the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Gansu province, China. METHODS: In this retrospective study, patients with laboratory-confirmed SARS-CoV-2 infection were consecutively enrolled from January 21, 2020 to February 11, 2020. The information on the epidemiological, clinical characteristics, laboratory tests, radiological features on admission, treatment and outcome were obtained with the final follow-up of March 13, 2020. On the basis of the median length of hospital stay, patients were further analyzed in two groups (long- vs. short-hospital stay). RESULTS: Of the 86 patients of COVID-19 in 11 cities of Gansu Province, the median hospital stay was 14.0 days (interquartile rang, 11.0-19.0 days). In the overall cohort, the median age was 41.0 years (interquartile rang, 31.0-54.3 years), and 48 (55.8%) patients were female. Forty (46.5%) had a history of exposure to epidemic regions, but none exposed to the Huanan seafood market in Wuhan. Common symptoms included fever (41, 47.7%), and cough (37, 43.0%). On admission, 30 (34.9%) and 58 (67.4%) patients had leukopenia and lymphopenia. According to chest CT scans, 53 (66.3%) of 80 patients showed bilateral pneumonia, and 19 (23.8%) of 80 patients showed unilateral pneumonia. Of the 15 asymptomatic cases, 10 (66.6%) cases were found CT findings of pneumonia. Besides, there were 65 (75.6%) patients with mild and moderate type of COVID-19. All 86 patients received antiviral and traditional Chinese medicine therapy, 53 (61.6%) received antibacterial therapy, and 3 (3.5%) patients received invasive ventilator mechanical ventilation. The proportion of patients received antibiotic treatment in long-hospital stay group was significantly higher than that in the short-hospital stay group (P=0.045). As of March 13, 2020, 84 (97.7%) patients were discharged, and two (2.3%) cases died. CONCLUSIONS: In the Gansu province cohort of 86 patients of COVID-19, most patients were with mild or moderate type, and most asymptomatic cases showed CT imaging findings of SARS-CoV-2 related pneumonia.

Effects of plasma ghrelin, obestatin, and ghrelin/obestatin ratio on blood pressure circadian rhythms in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease. Ghrelin and obestatin are two peptides from the same source but have opposite roles. Both of them can affect feeding and regulate vascular tune. The aim of this study was to investigate the relationship between plasma ghrelin, obestatin, the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS. METHODS: This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group), 30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group). Polysomnography (PSG) was performed in the OSAS group and over-weight group. Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring. The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P < 0.05). Plasma obestatin levels were lower in the over-weight group and OSAS group, but there was no significant difference among the three groups. The blood pressure in OSAS patients was higher, and there was a significant difference in all blood pressure parameters compared to the control group, and in the daytime average diastolic blood pressure (DBP), nocturnal average systolic blood pressure (SBP) and DBP, DBP variability values as compared to over-weight subjects. Furthermore, there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P < 0.01). Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters. In contrast, the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P < 0.05), as well as a strong positive correlation with the blood pressure variability values (P < 0.01). In multivariate analyses, AHI (P < 0.05) and G/O (P < 0.05) were independently related to SBP variability changes, while AHI (P < 0.05), G/O (P < 0.01) and BMI (P < 0.05) were independently related to DBP variability changes. CONCLUSIONS: Our data show plasma ghrelin and obestatin levels were related to obesity in OSAS. Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity. Moreover, the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.

No association between single nucleotide polymorphisms in pre-mirnas and the risk of gastric cancer in Chinese population.

OBJECTIVE(S): Accumulating evidence has demonstrated that miRNAs contribute to various genetic and epigenetic modifications in the pathogenesis of gastric cancer (GC). Recent studies focused on the four single nucleotide polymorphisms (SNPs) of pre-miRNAs including rs11614913, rs3746444, rs2910164, and rs2292832. It was suggested that these four SNPs were significantly associated with the risk of GC and were described as candidate susceptibility factors. However, the previous results show conflicting findings. The aim of this study was to investigate whether these four SNPs are associated with GC in Chinese Han population. MATERIALS AND METHODS: Genotype frequencies of these four SNPs of pre-miRNAs in 220 GC patients and 530 control subjects were performed using a PCR-RFLP assay. RESULTS: No significant differences in genotype and allelic distribution were found in these four SNPs between GC and control subjects in the Chinese Han population. However, we found that the allelic frequency distributions of control subjects in these four SNPs were significantly different from those of the Japanese and the Koreans (All the P<0.05). CONCLUSION: The four SNPs did not show any significant correlation with the development of GC in the Chinese Han population, based on the current study.