The RNA sequencing results revealed the expression of different genes and signaling pathways during chemotherapy resistance in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin's lymphoma that occurs primarily at extranodal sites and is commonly treated using chemotherapy and radiotherapy. PTCL is more malignant than other lymphoid tumors, resulting in a poor prognosis.The 5-year recurrence rate remains high, and there is a lack of standard treatment for patients with relapse-resistant disease. However, the molecular mechanisms underlying the resistance of peripheral T-cell lymphoma cells to chemotherapeutic drugs, as well as identifying strategies to overcome drug resistance remains unclear. In this study, we aimed to identify pivotal genes and signaling pathways associated with chemotherapy resistance in PTCL. METHODS: In this study, a total of 5 healthy controls and 7 clinical patients were enrolled; 4 patients were classified as chemotherapy sensitive, and 3 patients were classified as chemotherapy resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells. RNA sequencing was conducted on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, the expression patterns of the DEGs associated with the most enriched signaling pathways, with a special focus on cancer-related genes, were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral TCL patients. RESULTS: RNA sequencing (RNA-seq) analysis revealed 4063 differentially expressed genes (DEGs) in peripheral T-cell lymphoma specimens from patients with chemotherapy resistance, of which 1128 were upregulated and 2935 were downregulated. Subsequent quantitative gene expression analysis confirmed a differential expression pattern in all the libraries, with 9 downregulated genes and 10 upregulated genes validated through quantitative real-time PCR in 6 clinical specimens from patients with chemotherapy resistance. KEGG pathway analysis revealed significant alterations in several pathways, with 6 downregulated pathways and 9 upregulated pathways enriched in the DEGs. Notably, the TNF signaling pathway, which is extensively regulated, was among the pathways that exhibited significant changes. These findings suggest that DEGs and the TNF signaling pathway may play crucial roles in chemotherapy resistance in peripheral T-cell lymphoma. CONCLUSION: Our study revealed that the expression of specific genes, including TNFRSF1B, TRADD2, and MAP3K7, may play an important role in chemotherapy resistance in peripheral T-cell lymphoma. Moreover, we identified the downregulation of the TNF signaling pathway, a crucial pathway involved in cell survival, death, and differentiation, as a potential contributor to the development of chemotherapy resistance in peripheral T-cell lymphoma. These findings provide valuable insights into the molecular mechanisms underlying chemotherapy resistance and highlight potential targets for overcoming treatment resistance in this challenging disease.

M6A demethylase ALKBH5 regulates FOXO1 mRNA stability and chemoresistance in triple-negative breast cancer.

Resistance to chemotherapy is the main reason for treatment failure and poor prognosis in patients with triple-negative breast cancer (TNBC). Although the association of RNA N6-methyladenosine (m6A) modifications with therapy resistance is noticed, its role in the development of therapeutic resistance in TNBC is not well documented. This study aimed to investigate the potential mechanisms underlying reactive oxygen species (ROS) regulation in doxorubicin (DOX)-resistant TNBC. Here, we found that DOX-resistant TNBC cells displayed low ROS levels because of increased expression of superoxide dismutase (SOD2), thus maintaining cancer stem cells (CSCs) characteristics and DOX resistance. FOXO1 is a master regulator that reduces cellular ROS in DOX-resistant TNBC cells, and knockdown of FOXO1 significantly increased ROS levels by inhibiting SOD2 expression. Moreover, the m6A demethylase ALKBH5 promoted m6A demethylation of FOXO1 mRNA and increased FOXO1 mRNA stability in DOX-resistant TNBC cells. The analysis of clinical samples revealed that the increased expression levels of ALKBH5, FOXO1, and SOD2 were significantly positively correlated with chemoresistance and poor prognosis in patients with TNBC. To our knowledge, this is the first study to highlight that ALKBH5-mediated FOXO1 mRNA demethylation contributes to CSCs characteristics and DOX resistance in TNBC cells. Furthermore, pharmacological targeting of FOXO1 profoundly restored the response of DOX-resistant TNBC cells, both in vitro and in vivo. In conclusion, we demonstrated a critical function of ALKBH5-mediated m6A demethylation of FOXO1 mRNA in restoring redox balance, which in turn promoting CSCs characteristics and DOX resistance in TNBC, and suggested that targeting the ALKBH5/FOXO1 axis has therapeutic potential for patients with TNBC refractory to chemotherapy.

Survival analysis of patients with advanced non-small cell lung cancer receiving EGFR-TKI treatment of Yunnan in southwestern China: a real-world study.

Importance: Patients with EGFR mutations who have advanced-stage non-small cell lung cancer (NSCLC) already receive tyrosine kinase inhibitors (TKIs) as the standard first-line therapy. Notably, Yunnan is a regional high incidence area of lung cancer in the highlands with a high rate of rare EGFR mutations. Overall, lung cancer patients in Xuanwei may present a distinct subgroup globally. Recent studies suggested that the NSCLC cohort in Xuanwei harbored a significantly higher uncommon mutation rate. However, little was known about the clinicopathological features and treatment efficacy of EGFR-TKI in Yunnan NSCLC patients. Objective: This study aimed to investigate the clinical impact of histologic type on the survival outcomes of patients with stage IIIB and IV NSCLC receiving EGFR-TKI treatment of Yunnan in southwestern China. Methods: In this retrospective study, we enrolled advanced NSCLC patients (IIIB-IV) with EGFR mutations who were first diagnosed and treated at Yunnan Cancer hospital from January 2016 to December 2019. Sociodemographics, lifestyle, survival, and clinicopathological characteristics of the patients were collected. The Kaplan-Meier method was used to assess the OS and PFS of patients. An analysis of prognostic factors was conducted using Cox regression. Results: A total of 468 eligible patients were included. The median progression-free survival (PFS) and overall survival(OS) were 11.30(95% CI, 10.12-12.48) months and 30.30(95% CI, 26.24-34.36) months. Based on survival analysis among all the patients,females(HR=0.815;95% CI:0.671-0.989; P=0.017), Xuanwei origin (HR=0.776; 95% CI: 0.609-0.989; P=0.040), sample types(HR=0.780; 95% CI: 0.642-0.947; P=0.012) had a longer PFS. Multivariable analysis showed that only the sample type was an independent factor on median PFS with EGFR-TKI therapy. Patients less than 60 years old (HR=1.433; 95% CI:1.134-1.812, P=0.003)had better OS, but objectives with BMI≥24kg/m2(HR=0.653; 95% CI: 0.500-0.864; P=0.002), females(HR=0.776; 95% CI:0.613-0.982; P=0.035)and patients with tissue sample type (HR=0.760; 95% CI:0.600-.0961; P=0.022) had better OS. Notably, subgroup analysis of our study also found that PFS was significantly better in patients with G719X, L861Q, S768I, G719X+L861Q, and G719X+S768I in Xuanwei than classical mutation ones, including 19-Del and L858R (median 22.7 vs. 12.0 months, HR=0.523, P=0.010), while PFS was inferior in patients with rare mutations of EGFR in non-Xuanwei than the classical mutation ones (median 5.10 vs. 11.10 months, HR=1.760, P=0.015). Conclusion: NSCLC patients in Yunnan displayed a unique EGFR mutation profile, especially a higher prevalence of EGFR uncommon and compound mutations subtype. This study indicates prognostic factors of NSCLC treated with EGFR-TKI in Yunan and Xuanwei. This study will provide new clinical evidence for EGFR-TKI-targeted therapy in patients with rare EGFR mutations in China and worldwide. More researchs were needed for NSCLC EGFR-TKI therapy and medical insurance policy-making in Yunnan, Xuanwei area and uncommon especially.

Effects of lncRNA HOXA11-AS on Sevoflurane-Induced Neuronal Apoptosis and Inflammatory Responses by Regulating miR-98-5p/EphA4.

Objective: To explore the molecular mechanism of sevoflurane-induced neurotoxicity and to determine whether lncRNA HOXA11-AS affects sevoflurane-induced neuronal apoptosis and inflammation by regulating miR-98-5p/EphA4. Methods: Morris water maze (MWM) test was used to detect the learning and memory ability of rats, HE staining was used to observe hippocampal pathology, TUNEL staining was used to detect the level of neuronal apoptosis, and RT-qPCR was used to detect the expression of HOXA11-AS, miR-98-5p, IL-6, IL-1ß, and TNF-α. At the same time, the contents of IL-6, IL-1ß, and TNF-α in serum were detected by ELISA. The expressions of apoptosis-related proteins EphA4, Bax, Cleaved caspase 3, and Bcl-2 were detected by Western blot. The dual-luciferase gene reporter verified the targeting relationship between HOXA11-AS and miR-98-5p and the targeting relationship between miR-98-5p and EphA4. Results: The expression of HOXA11-AS was observed in sevoflurane-treated rats or cells and promoted neuronal apoptosis and inflammation. HOXA11-AS was knocked out alone, or miR-98-5p was overexpressed which attenuates neuronal apoptosis and inflammatory inflammation after sevoflurane treatment. Furthermore, knockdown of HOXA11-AS alone was partially restored by knockdown of miR-98-5p or overexpression of EphA4. Conclusion: Inhibition of lncRNA HOXA11-AS attenuates sevoflurane-induced neuronal apoptosis and inflammatory responses via miR-98-5p/EphA4.

Mutational characteristics of Chinese Han and ethnic minorities in southwestern China: a propensity score matched analysis.

Background: In China, there has never been a comprehensive analysis of lung cancer-associated genetic mutations focused on ethnic minorities in the southwestern region. Our study aimed to provide valuable information on lung cancer-associated genetic alterations for cancer diagnosis and treatment, especially in ethnic minorities. Methods: Retrospective data acquisition was conducted spanning 3 years (2016.01-2019.06) among all patients who were diagnosed with lung cancer at the Third Affiliated Hospital of Kunming Medical University Hospital. A total of 5,167 patients including 373 ethnic minorities were included in this study. Propensity score matching (PSM) was used to eliminate the bias between Han and other ethnic minorities, including gender, age, smoking history, metastasis status, clinical stage, histological type, sample type, region, and Xuanwei origin. All tests were two-tailed, and significance was defined as P less than 0.05. Results: In terms of the prevalence of EGFR, EGFR L858R, EGFR T790M, ROS1, RET, MET, BRAF, and ERBB2 mutations, there was no significant difference among ethnic groups in Yunnan Province (P>0.05). A higher proportion of EGFR 19 deletion was observed in Hui patients with lung cancer compared with patients of other ethnicities in Yunnan (P=0.048). The prevalence of KRAS mutations was higher in Hani (17.65%, 3/17) and Han patients (11.44%, 80/699) than that in other Yunnan ethnicities (6.04%, 9/149; P=0.07). In Hui patients, ALK fusion was correlated with a history of non-smoking and male gender. In Bai patients, BRAF mutation was also correlated with a history of non-smoking. In all ethnic groups, EGFR mutation was more frequent in women. Conclusions: This study is the first in-depth large case-control study on genetic mutation profiles among multi-ethnic patients in southwestern China, especially focused on ethnic minorities in this area. Our study may facilitate the understanding of the etiology of this malignant disease and consequently help to reduce the incidence of lung cancer in Yunnan ethnic minority areas.

A neutral polysaccharide from Ophiocordyceps lanpingensis restrains cisplatin-induced nephrotoxicity.

Ophiocordyceps lanpingensis is an edible mushroom distributed over the south-eastern part of the Tibet Plateau, which is also recognized as an effective ethnomedicine to alleviate diseases. This study explored the effects of a kind of Ophiocordyceps lanpingensis neutral polysaccharide (ONP) on RAW264.7 macrophages and cisplatin-induced nephrotoxicity. The results showed that ONP relieved the inflammatory response of RAW264.7 macrophages by increasing the expression level of anti-inflammatory factor IL-10. Furthermore, ONP treatment significantly prolonged the survival of the mice treated by cisplatin through decelerating pathological progress and alleviating damaged functions of the kidneys. Compared with the cisplatin group, ONP reduced the oxidative stress of the renal cells and the expression levels of pro-inflammatory factors. Apoptosis of renal cells was also weakened in the ONP treatment group. These findings indicated that ONP alleviated cisplatin nephrotoxicity mainly by inhibiting oxidative stress, inflammation, and apoptosis in the kidneys, underscoring the potential of ONP supplementation to alleviate the side effects of cisplatin chemotherapy.

Blood Tumor Mutational Burden as a Predictive Biomarker in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).

This study was designed to investigate the impact of blood tumor mutational burden (bTMB) on advanced NSCLC in Southwest China. The relationship between the tTMB estimated by next-generation sequencing (NGS) and clinical outcome was retrospectively analyzed in tissue specimens from 21 patients with advanced NSCLC. Furthermore, the relationship between the bTMB estimated by NGS and clinical outcome was retrospectively assessed in blood specimens from 70 patients with advanced NSCLC. Finally, 13 advanced NSCLC patients were used to evaluate the utility of bTMB assessed by NGS in differentiating patients who would benefit from immunotherapy. In the tTMB group, tTMB ≥ 10 mutations/Mb was related to inferior progression-free survival (PFS) (hazard ratio [HR], 0.30; 95% CI, 0.08-1.17; log-rank P = 0.03) and overall survival (OS) (HR, 0.30; 95% CI, 0.08-1.16; log-rank P = 0.03). In the bTMB group, bTMB ≥ 6 mutations/Mb was associated with inferior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank P < 0.01) and OS (HR, 0.31; 95% CI, 0.14-0.7; log-rank P < 0.01). In the immunotherapy section, bTMB ≥ 6 mutations/Mb was related to superior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank P < 0.01) and objective response rates (ORRs) (bTMB < 6: 14.2%; 95% CI, 0.03-1.19; bTMB ≥ 6: 83.3%; 95% CI, 0.91-37.08; P = 0.02). These findings suggest that bTMB is a validated predictive biomarker for determining the clinical outcome of advanced NSCLC patients and may serve as a feasible predictor of the clinical benefit of immunotherapies (anti-PD-1 antibody) in the advanced NSCLC population in Yunnan Province.

Unique Profile of Driver Gene Mutations in Patients With Non-Small-Cell Lung Cancer in Qujing City, Yunnan Province, Southwest China.

OBJECTIVE: Qujing City, Yunnan Province, China, has a high incidence of lung cancer and related mortality. The etiology of NSCLC in Qujing area and distribution of associated molecular aberrations has not been fully elucidated. This study aimed to reveal the profile of driver gene mutations in patients with non-small-cell lung cancer (NSCLC) in Qujing and explore their relationships with clinicopathological characteristics. METHODS: In this study, the mutation profiles of NSCLC driver genes, including EGFR, ALK, ROS1, KRAS, BRAF, RET, MET, HER2, NRAS, and PIK3CA, were investigated in patients with NSCLC from Qujing and compared with those from other regions in Yunnan Province. The associations between molecular mutations and clinicopathological characteristics were further analyzed. RESULTS: A distinct profile of driver gene mutations was discovered in patients with NSCLC from Qujing. Interestingly, a higher proportion of EGFR compound mutations, including G719X + S768I (19.65% vs 3.38%, P < 0.0001) and G719X + L861Q (21.10% vs 2.82%, P < 0.0001), was observed in patients with NSCLC in Qujing compared with patients in non-Qujing area, besides significantly different distributions of EGFR (46.01% vs. 51.07%, P = 0.0125), ALK (3.17% vs. 6.97%, P = 0.0012), ROS1 (0.5% vs. 2.02%, P = 0.0113), and KRAS (23.02% vs. 7.85%, P < 0.0001). Further, EGFR compound mutations were more likely associated with the occupation of patients (living/working in rural areas, e.g., farmers). Moreover, KRAS G12C was the dominant subtype (51.11% vs 25.00%, P = 0.0275) among patients with NSCLC having KRAS mutations in Qujing. CONCLUSIONS: Patients with NSCLC in Qujing displayed a unique profile of driver gene mutations, especially a higher prevalence of EGFR compound mutations and dominant KRAS G12C subtype, in this study, indicating a peculiar etiology of NSCLC in Qujing. Therefore, a different paradigm of therapeutic strategy might need to be considered for patients with NSCLC in Qujing.

Oncogenic Genetic Alterations in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

PURPOSE: To investigate the impact of oncogenic genetic alterations (GAs) on non-small-cell lung cancer (NSCLC) in southwestern China. PATIENTS AND METHODS: We first collected 579 pathologically confirmed NSCLC specimens and then used next-generation sequencing (NGS) to evaluate the DNA samples for GAs. Both the tissue and plasma samples were provided by 28 patients. Furthermore, subgroup analyses based on sample type, concordance, and GA type were carried out. RESULTS: GAs were detected by NGS in 61.8% (358/579) of patients. Two hundred and twenty-nine patients (39.6%) harbored EGFR mutations, 63 (10.9%) harbored KRAS mutations, 13 (2.2%) harbored BRAF mutations, 30 (5.18%) harbored ALK fusions, and 13 (2.2%) had ROS1 fusions. We found that females (p < 0.01), nonsmokers (p < 0.001), adenocarcinoma (p < 0.001), and tissue (p = 0.03) had a relatively high EGFR mutation rate. Notably, NSCLC patients from Xuanwei had a significantly different mutational pattern for EGFR in comparison with that of non-Xuanwei patients (higher G719X + S768I mutations and multiple gene alterations, but fewer exon 19 deletion mutations and single gene alterations). We found that adenocarcinoma (p = 0.02), family history of malignancy (p = 0.03), Xuanwei origin (p < 0.001), and tissue (p = 0.04) were associated with a higher number of KRAS mutations. Subgroup analysis showed that ALK (p < 0.001) and ROS1 (p < 0.05) fusions and rare EGFR mutations (p < 0.001) were associated with non-Han ethnic patients. CONCLUSION: Yunnan NSCLC patients from Xuanwei and non-Han ethnic patients had an obviously unique prevalence of GAs.

Tumor Mutational Burden and PD-L1 Expression in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

PURPOSE: To explore the impact between the tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression on NSCLC in the Yunnan region of southwestern China. PATIENTS AND METHODS: Seventy-one NSCLC specimens that were pathologically confirmed were collected at first. The TMB and driver genetic alterations were evaluated accordingly by next-generation sequencing (NGS). Afterwards, clinical parameters and tumor PD-L1 expressions were collected. Finally, the relationship between TMB, PD-L1 expression and clinical outcome was evaluated. RESULTS: The median TMB was 5 (0.6-49) mutations/Mb by our NGS panel and the majority of patients (63/71, 88.7%) did not receive immunotherapy. The progression-free survival (PFS) was longer in TMB-low patients versus TMB-high ones (median 18.0 vs. 9.0 months, hazard ratio = 0.34, 95% confidence interval 0.14 to 0.84, p = 0.02) and the cut-off value was 10 mutations/Mb. The overall survival (OS) was longer in TMB-low patients vs. TMB-high ones (median 21.0 vs. 10.0 months, HR = 0.32, 95% CI 0.12 to 0.82, p = 0.02). Notably, our study also found that, excluding the eight patients with immunotherapy, the PFS was longer in patients with TMB-low vs. TMB-high (median 19.0 vs. 8.0 months, HR = 0.11, 95% CI 0.03 to 0.39, p < 0.01) and the OS was longer in TMB-low patients vs. TMB-high (median 21.0 vs 10.0 months, HR = 0.12, 95% CI 0.03 to 0.42, p < 0.01). CONCLUSION: TMB was a valid and independent prognostic biomarker for NSCLC patients' clinical outcome and comprehensive screening of TMB based on NGS is recommended for individualized treatment strategies in Yunnan population.

Ophiocordyceps lanpingensis polysaccharides attenuate pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with growing prevalence. Currently available therapies for treating IPF are not desirable due to the limited efficacy and multiple side effects. Ophiocordyceps lanpingensis is one strain of entomogenous fungi, which has been collected from the eastern part of the Himalayas. This study revealed that O. lanpingensis polysaccharides (OLP) could attenuate bleomycin (BLM) induced lung fibrosis in mice. Results showed that OLP treatments significantly reduced BLM-induced collagen deposition and decreased the accumulation of macrophages. The oxidative stress of the lung was alleviated by OLP. The expression levels of pro-inflammatory and pro-fibrogenic factors in OLP groups were also decreased compared with those in the BLM group, which might explain the improved alveolar integrity and function in the OLP treated groups. Our findings indicated that OLP treatment could alleviate pulmonary fibrosis progression mainly through reducing the recruitment of macrophages to the lungs.

MicroRNA-195 suppresses the progression of lung adenocarcinoma by directly targeting apelin.

BACKGROUND: Apelin plays an important role in many types of tumors. We aimed to identify the effects of miR-195 on inhibiting apelin and clarify the regulating mechanism of miR-195-apelin in lung adenocarcinoma cells. METHODS: We detected the expression levels of apelin and miR-195 in lung adenocarcinoma tissues and lung cancer cell lines using Western blotting and quantitative reverse transcription PCR assay, respectively. Luciferase reporter assay was used to confirm the target gene of miR-195. The effects of miR-195 and apelin on the proliferation and cell cycle of lung adenocarcinoma cells were assessed by methyl thiazolyl tetrazolium and colony formation assays, and flow cytometry. Wound-healing and transwell invasion experiments were employed to examine cellular migration and invasion. A tumor xenograft model was then used to investigate the role of miR-195 on tumor growth in vivo. RESULTS: The expression level of apelin and miR-195 showed an inverse correlation in lung adenocarcinoma tissues and cell lines. Luciferase reporter assay suggested that miR-195 directly targets apelin messenger RNA. Overexpression of miR-195 significantly inhibited the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and suppressed tumor growth in vivo. Further analysis revealed that apelin is one of the functional target genes of miR-195, and the overexpression of apelin efficiently inhibits the promotion of cell proliferation and invasion mediated by miR-195 mimics in lung adenocarcinoma cells. CONCLUSIONS: Our data constitute evidence that miR-195 inhibits lung adenocarcinoma cell proliferation and invasion though targeting apelin and provides novel insight into the mechanism underlying the development of lung adenocarcinoma.

Epidermal growth factor receptor T790M mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China.

To explore the effect of epidermal growth factor receptor (EGFR) T790M mutation status on non-small cell lung cancer (NSCLC) in Yunnan province of southwestern China. First, this study used the super amplification refractory mutation system (Super ARMS) polymerase chain reaction (PCR) and Droplet Digital PCR (dd PCR) to evaluate the T790M gene mutation, in plasmatic ctDNA samples from 212 cases of NSCLC. The association between T790M mutations and clinical parameters were further explored. Next, to investigate the mechanism of drug resistance that resulted from T790M mutation, subgroup analyses according to duration of medicine (EGFR-TKIs) were carried out. Finally, we also evaluate the effectiveness of blood-based circulating tumor DNA (ctDNA) on detecting the T790M mutation by calculating Super ARMS's detection efficiency. We found that the T790M mutation rate was 8.4% (18/212) in overall patients. The T790M mutation was more frequent in patients with brain metastasis 30.0% (12/40) (p < 0.01). We found that post-TKI samples 42.8% (15/35) were associated with a higher T790M mutation rate (p < 0.01). Subgroup analysis showed that the duration of TKI therapy for 6 to 10 months 66.6% (8/12) (p < 0.01) and >10 months 75.0% (9/12) (p < 0.01) were also associated with a higher T790M mutation rate. Super ARMS's sensitivity, specificity, PPV, NPV, and accuracy were 100.0%, 99.4%, 94.7%, 100.0%, and 99.5% respectively. Generally, the EGFR-T790M mutation was more common in NSCLC patients with brain metastasis and those who received TKI therapy for more than 6 months. Moreover, Super ARMS is a sensitive, efficient, and practical clinic method for dynamically monitoring T790M mutation status and effectively guiding clinic treatment.

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report.

BACKGROUND: Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients. CASE PRESENTATION: In June 2016, a 52-year-old Chinese man presented with human immunodeficiency virus and lung adenocarcinoma (T1bN3M1b). From November 2016 to December 2016, systemic chemotherapy and palliative radiotherapy for bone metastasis of femoral neck were carried out, but the tumor progressed. In January 2017, after immunochemistry detection of programmed death-1 and programmed death-ligand 1 expression (both > 50%), pembrolizumab was started. Three weeks after pembrolizumab, we combined stereotactic body radiotherapy for the primary lung tumor. He received no comfort and his CD4 lymphocyte count was stable. Human immunodeficiency virus-ribonucleic acid remained below the limits of detection. In March 2017, after three cycles of pembrolizumab and 5 weeks of stereotactic body radiotherapy therapy, he suddenly presented with palpitations. Emergency computed tomography scanning showed massive pericardial effusion and interstitial pneumonia. So we interrupted the pembrolizumab use and initiated treatment with prednisolone 1 mg/kg; however, the tumor progressed. Then, his CD4 lymphocyte count declined. Finally he died in June 2017 due to dyscrasia. CONCLUSIONS: Pembrolizumab combined with SBRT therapy for patients with human immunodeficiency virus infection and non-small cell lung cancer may lead to serious immune-related adverse events and more clinical trials are needed.

Protective Effects of Ophiocordyceps lanpingensis on Glycerol-Induced Acute Renal Failure in Mice.

OBJECTIVE: Oxidative stress and immune response are associated with acute renal failure (ARF). Ophiocordyceps lanpingensis (OL) might be an antioxidant and immunopotentiator. In this study, we explored the protective effects of OL on glycerol-induced ARF. METHODS: Male mice were randomly divided into four groups, specifically, glycerol-induced ARF model group, low-dose OL-treated group (1.0 g/kg/d), high-dose OL-treated group (2.0 g/kg/d), and control group. Renal conditions were evaluated using kidney index, serum creatinine (Cr), blood urea nitrogen (BUN), and histological analysis. Rhabdomyolysis was monitored using creatine kinase (CK) level. Oxidative stress was determined using kidney tissue glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Immune status was evaluated using immune organ indices and immunoglobulin G (IgG) level. RESULTS: OL could relieve renal pathological injury and decrease the abnormal levels of kidney index, serum Cr, CK, BUN, and MDA, as well as increase the immune organ indices and the levels of IgG, GSH, and SOD. Treatment with a high dose of OL had more positive therapeutic effects on ARF than using a low dose of OL. CONCLUSION: OL could ameliorate renal dysfunction in glycerol-induced ARF in mice by inhibiting oxidative stress and enhancing immune response.

Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China.

To investigate the Epidermal Growth Factor Receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) in Yunnan province in southwestern China, we detected EGFR mutation by Amplification Refractory Mutation System (ARMS) polymerase chain reaction (PCR) using DNA samples from 447 pathologically confirmed NSCLC specimens (175 tissue, 256 plasma and 16 cytologic samples). The relationship between EGFR mutations and demographic and clinical factors were further explored. Subgroup analyses according to sample type (tissue and plasma) and histological type (adenocarcinoma) were done. We found the mutation rate was 34.9% in overall patients (42.3%, 29.7%, and 37.5% for tissue, plasma, and cytologic samples respectively). We found female (p < 0.0001), no smoking (p = 0.001), adenocarcinoma (p < 0.0001), and tissue specimen (p = 0.026) were associated with higher EGFR mutation rate. The most common mutations were exon 19 deletions (40%) and L858R point (30%) mutation. Interestingly, NSCLC patients from Xuanwei harbored a strikingly divergent mutational pattern for EGFR when compared with non-Xuanwei patients (higher G719X, G719X+S768I mutations, but lower 19 deletion and L858R mutations). Generally, EGFR mutation rate and pattern in Yunnan province was in accord with other Asian populations. However, Xuanwei subgroup showed strikingly divergent EGFR mutation spectrum from other general population. Our analysis also indicated that cftDNA analysis for EGFR mutations detection was feasibility for the patients lacking sufficient tissue for molecular analyses.

[Specific microRNA expression profiles of lung adenocarcinoma in Xuanwei region and bioinformatic analysis for predicting their target genes and related signaling pathways].

OBJECTIVE: To identify differentially expressed microRNAs (miRNAs) related to lung adenocarcinoma in Xuanwei region and predict their target genes and related signaling pathways based on bioinformatic analysis. METHODS: High-throughput microarray assay was performed to detect miRNA expression profiles in 34 paired human lung adenocarcinoma and adjacent normal tissues (including 24 cases in Xuanwei region and 10 in other regions). Gene ontology and KEGG pathway analyses were used to predict the target genes and the regulatory signaling pathways. RESULTS: Thirty-four miRNAs were differentially expressed in lung adenocarcinoma tissues in cases in Xuanwei region as compared with cases in other regions, including 23 upregulated and 11 downregulated miRNAs. The predicted target genes included GF, RTK, SOS, IRS1, BCAP, CYTOKINSR, ECM, ITGB, FAK and Gbeta;Y involving the PI3K/Alt, WNT and MAPK pathways. CONCLUSION: The specific microRNA expression profiles of lung adenocarcinoma in cases found in Xuanwei region allow for a better understanding of the pathogenesis of lung adenocarcinoma in Xuanwei. The predicted target genes may involve the PI3K/Alt, WNT and MAPK pathways.