Clinical Features and Management of Lung Cancer During Pregnancy: A Narrative Review Based on Reported Cases.

This review aims to provide a summary of the clinical characteristics and outcomes of lung cancer during pregnancy. A comprehensive literature search yielded 93 cases of lung cancer during pregnancy from 1953 to 2022, with an average maternal age of ∼34 years old. The initial symptoms reported were often nonspecific, such as cough, dyspnea, and chest pain. Cancer-related treatments, including surgery, radiotherapy, chemotherapy, and tyrosine kinase inhibitors, have shown beneficial effects on maternal outcomes. A majority of the newborns were born without malformation or diseases, but extended follow-up remains necessary. Early diagnosis of lung cancer is imperative for reducing the risks of placental and fetal metastasis and enhancing overall survival.

[Analysis of CSF3R Gene Mutations and Clinical Characteristics in Patients with t(8;21) Acute Myeloid Leukemia].

OBJECTIVE: To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters. METHODS: The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed. RESULTS: Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes（P <0.001）. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037). CONCLUSION: There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1ß, IL-17, and transforming growth factor (TGF)-ß1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1ß levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1ß levels. These findings may be of diagnostic value.

Changes of circulating biomarkers of inflammation and glycolipid metabolism by CPAP in OSA patients: a meta-analysis of time-dependent profiles.

Background: Continuous positive airway pressure (CPAP) is the first-line therapy for moderate-to-severe obstructive sleep apnea (OSA). Specifying timing of CPAP benefits on OSA-related biomarkers will help to assess the effectiveness of CPAP and to optimize the treatment strategies. Purpose: To explore the time-dependent changes of circulating biomarkers to CPAP treatment in patients with OSA, including inflammatory biomarkers [C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and glycolipid metabolic biomarkers [fasting blood glucose (FBG), fasting insulin (FINS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG)]. Methods: Searches of PubMed and Embase database were completed. Two independent reviewers extracted data from 68 included studies. A meta-analysis was conducted using a random-effect (or fixed-effect) model and standardized mean difference (SMD) model. The timing profiles of circulating biomarkers changes of inflammation and glycolipid metabolism were analyzed based on different CPAP duration, that is, short-term (<3 months), mid-term (3-6 months), and long-term (⩾6 months). Results: Those first improved by short-term treatment include CRP [SMD: 0.73, 95% confidence interval (CI): 0.15-1.31; p = 0.014], TNF-α [SMD: 0.48 (95% CI: 0.10-0.86; p = 0.014)], FBG [SMD: 0.32 (95% CI: 0.07-0.57; p = 0.011)], and LDL [SMD: 0.40 (95% CI: 0.18-0.62; p = 0.000)]. Those first improved by the mid-term or long-term treatment include HDL [SMD: -0.20 (95% CI: -0.36 to -0.03; p = 0.018)] and TC [SMD: 0.20 (95% CI: 0.05-0.34; p = 0.007)]. There were insignificant changes for TG and FINS after short or long CPAP. Conclusion: Our results imply that changes of circulating biomarkers for patients with OSA under CPAP treatment have a time-dependent profile.

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke.

Epidemiologic studies have shown that the fine particulate matter 2.5 (PM2.5) exaggerates chronic airway inflammation involving in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Surfactant proteins (SPs) decreases significantly related to airflow limitation and airway inflammation. However, how to restore the reduction of SPs levels in airway inflammation exposed to PM2.5 has not been well understood. In the present study, the SPs including SPA, SPB, SPC and SPD levels in bronchoalveolar lavage fluid (BALF) were detected from patients with stable COPD. Rats were exposed to cigarette smoke and PM2.5. After given with Surfaxin, the expression of SPs, protein kinase C (PKC) and tight junction protein (ZO-1) in lung tissue and the levels of C-reactive protein (CRP) and fibrinogen (FIB) in plasma was observed. The results showed that SPA, SPB and SPD were significantly lower than those of the control group (p < 0.01). PM2.5 aggravated smoking-induced airway inflammation and oxidative stress demonstrated by pathological changes of lung tissue and increased levels of CRP and PKC in vivo. PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs.

Genetic characteristics of a patient with multiple primary cancers: A case report.

BACKGROUND: Two or multiple primary malignant neoplasms (MPMNs) rarely occur in the same patient. It has been reported that MPMNs are easily misdiagnosed as the recurrence or metastasis of malignancies in clinical practice, affecting the choice of treatment for the patients, thereby resulting in the delay of optimal diagnosis. Next generation sequencing (NGS) can be used to distinguish between multiple primary lung cancers and intrapulmonary metastasis, and may distinguish the origin of tumours in different sites of the body. CASE SUMMARY: We report the case of 66-year-old woman who suffered from different malignant neoplasms in the rectum and esophageal and gastrointestinal tract. The first neoplasm rectal adenocarcinoma was diagnosed and removed in 2016. The second and third lesions were diagnosed with esophageal squamous-cell carcinoma (ESCC) and gastrointestinal stromal tumour (GIST), respectively, in 2019. Next-generation whole exome sequencing was performed on the tissue specimens of rectal carcinoma, esophageal cancer, GIST, and white blood cells to investigate the relationship between malignancies at different timeframe and determine whether the ESCC and GIST evolved from the rectal adenocarcinoma. Mutations including v-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog, adenomatosis polyposis coli, and mothers against decapentaplegic homolog 4 were detected in rectal adenocarcinoma sample, mast/stem cell growth factor receptor was detected in GIST tissue, and lysine methyltransferase 2D was detected in ESCC specimen. Overall, ESCC and GIST were not genetically evolved from rectal adenocarcinoma, and this patient did not have a trunk driven clone. CONCLUSION: NGS is an effective tool to study clonal evolution of tumours and distinguish between MPMNs and intrapulmonary metastasis.

Transcriptomics Analysis Identifies the Presence of Upregulated Ribosomal Housekeeping Genes in the Alveolar Macrophages of Patients with Smoking-Induced Chronic Obstructive Pulmonary Disease.

BACKGROUND AND AIMS: Alveolar macrophages (AM) play a crucial role in the development of chronic obstructive pulmonary disease (COPD). The role that AM plays in the molecular pathways and clinical phenotypes associated with tobacco-related emphysema remain poorly understood. Thus, we investigated the transcriptomic profile of AM in COPD patients with a history of smoking and explored the molecular mechanisms associated with enriched pathways and hub genes. METHODS: Four data sets (GSE2125, GSE8823, GSE13896 and GSE130928) were retrieved from the GEO Database. A total of 203 GEO samples (GSM) were collated for this study. About 125 of these cases were classified as smokers (91 as healthy non-COPD smokers and 34 as COPD smokers). Based on the bioinformatics obtained using the R3.6.1 program, the data were successively adopted for differential genetic expression analysis, enrichment analysis (EA), and then protein-protein interaction analysis (PPI) in a STRING database. Finally, Cytoscape 3.8 software was used to screen the hub genes. A further data analysis was performed using a set of 154 cases, classified as 64 healthy non-smokers and 91 as healthy smokers. The same procedures were used as for the COPD dataset. RESULTS: When comparing the data pertaining to COPD-smokers and non-COPD smokers, the top ten genes with the greatest transcriptional differences were found to be NADK, DRAP1, DEDD, NONO, KLHL12, PRKAR1A, ITGAL, GLE1, SLC8A1, SVIL. A GSEA (Gene Set Enrichment Analysis) revealed that these genes manifested an up-regulated ribosomal pathway in contrast with other genes that exhibited an extensive down-regulated pathway. The hub genes were mainly genes encoding ribosomal subunits through PPI. Furthermore, it was found that there is a narrow transcriptional difference between healthy non-smokers and non-COPD smokers and the hub genes identified here are mainly members of the chemokines, including CCL5, CCR5, CXCL9 and CXCL11. CONCLUSION: An elevated activity of the ribosome pathway in addition to the increased expression of ribosomal housekeeping genes (also known as hub genes) were identified with COPD-smokers, and these have the potential to cause a wide range of downstream pathogenetic effects. As for the preclinical phase, non-COPD smokers were found to be characterized by enriched pathways of several chemokines in AM.

Moderate to severe OSA screening based on support vector machine of the Chinese population faciocervical measurements dataset: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) has received much attention as a risk factor for perioperative complications and 68.5% of OSA patients remain undiagnosed before surgery. Faciocervical characteristics may screen OSA for Asians due to smaller upper airways compared with Caucasians. Thus, our study aimed to explore a machine-learning model to screen moderate to severe OSA based on faciocervical and anthropometric measurements. DESIGN: A cross-sectional study. SETTING: Data were collected from the Shanghai Jiao Tong University School of Medicine affiliated Ruijin Hospital between February 2019 and August 2020. PARTICIPANTS: A total of 481 Chinese participants were included in the study. PRIMARY AND SECONDARY OUTCOME: (1) Identification of moderate to severe OSA with apnoea-hypopnoea index 15 events/hour and (2) Verification of the machine-learning model. RESULTS: Sex-Age-Body mass index (BMI)-maximum Interincisal distance-ratio of Height to thyrosternum distance-neck Circumference-waist Circumference (SABIHC2) model was set up. The SABIHC2 model could screen moderate to severe OSA with an area under the curve (AUC)=0.832, the sensitivity of 0.916 and specificity of 0.749, and performed better than the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male gender) questionnaire, which showed AUC=0.631, the sensitivity of 0.487 and specificity of 0.772. Especially for asymptomatic patients (Epworth Sleepiness Scale <10), the SABIHC2 model demonstrated better predictive ability compared with the STOP-BANG questionnaire, with AUC (0.824 vs 0.530), sensitivity (0.892 vs 0.348) and specificity (0.755 vs 0.809). CONCLUSION: The SABIHC2 machine-learning model provides a simple and accurate assessment of moderate to severe OSA in the Chinese population, especially for those without significant daytime sleepiness.

A narrative review of exploring potential salivary biomarkers in respiratory diseases: still on its way.

Saliva is abundant with proteins, metabolites, DNA, and a diverse range of bacterial species. During the past two decades, saliva has emerged as a novel diagnostic and evaluation medium for several diseases. Collection of saliva samples is simple, minimally invasive, and convenient even in infants, children, and patients with anxious. Furthermore, with the development of hypersensitive techniques [e.g., microsensor arrays, enzyme-labeled immunosensors, nanoparticle-labeled immunosensors, capacitive or impedimetric immunosensors, magneto immunosensors, field effect transistor immunosensors, and surface enhanced Raman spectroscopy (SERS)], the sensitivity and accuracy of saliva diagnostic procedures have been improved. Nowadays, saliva has been used as a potential medium for several disease diagnosis and assessment, such as periodontitis, caries, cancers, diabetes mellitus, and cardiovascular diseases. Saliva has been used widely for studying microbiomics, genomics, transcriptomics, proteomics, and metabolomics of respiratory diseases, however, the use of salivary biomarkers for the diagnosis, prognosis, and monitoring of respiratory disease is still in its infancy. Herein, we review the progress of research on salivary biomarkers related to several respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), pneumonia, tuberculosis (TB), Langerhans cell histiocytosis (LCH) and cystic fibrosis (CF). Furthermore, several limitations of saliva test such as the lack of standard protocol for saliva collection and reasonable reference values for saliva test are also mentioned in this review.

Bronchial Variation: Anatomical Abnormality May Predispose Chronic Obstructive Pulmonary Disease.

Noxious particulate matter in the air is a primary cause of chronic obstructive pulmonary disease (COPD). The bronchial tree acts to filter these materials in the air and preserve the integrity of the bronchi. Accumulating evidence has demonstrated that smoking and air pollutants are the most prominent risk factors of COPD. Bifurcations in the airway may act as deposition sites for the retention of inhaled particles, however, little is known concerning the impacts of abnormalities of the bronchial anatomy in the pathogenesis of COPD. Studies have reported significant associations between bronchial variations and the symptoms in COPD. In particular, it has been shown that bronchial variations in the central airway tree may contribute to the development of COPD. In this review, we identified three common types of bronchial variation that were used to formulate a unifying hypothesis to explain how bronchial variations contribute to the development of COPD. We also investigated the current evidence for the involvement of specific genes including fibroblast growth factor 10 (Fgf10) and bone morphogenetic protein 4 (Bmp4) in the formation of bronchial variation. Finally, we highlight novel assessment strategies and opportunities for future research of bronchial variations and genetic susceptibility in COPD and comorbidities. Our data strongly highlight the role of bronchial variations in the development, complications, and acute exacerbation of COPD.

Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI: A case report.

RATIONALE: The incidence of nonsmall cell lung cancer (NSCLC) is high. Most nonsmall cell lung cancers have undergone multiple metastases at the time of initial diagnosis, and the 5 year survival rate is low. At present, comprehensive treatments, including systemic chemotherapy, targeted therapy, antiangiogenic therapy, and immunotherapy, prolong the survival of patients with advanced NSCLC. Herein, we report a case of NSCLC with long-term survival. PATIENT CONCERNS: A 61-year-old woman complained of dry cough and shortness of breath and visited our hospital in July 2011. Imaging examination revealed a left upper lung mass with multiple metastases to the liver, adrenal gland, and bone. DIAGNOSES: Stage IVB (cT2aN3M1c) lung adenocarcinoma was diagnosed, with multiple metastases of the lymph nodes, liver, adrenal gland, and bone. INTERVENTIONS AND OUTCOMES: The patient received systemic chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor-targeted therapy, and has survived for more than 9 years. LESSONS: The patient benefited from maintenance chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor treatment and achieved long-term survival.

Angiotensin-(1-7) Rescues Chronic Intermittent Hypoxia-Aggravated Transforming Growth Factor-ß-Mediated Airway Remodeling in Murine and Cellular Models of Asthma.

Renin-angiotensin system (RAS) is involved in TGF-ß-mediated epithelial-to-mesenchymal transition (EMT) and is responsible for airway remodeling in refractory asthma. Obstructive sleep apnea (OSA), which affects RAS activity, is a risk factor for refractory asthma. We aimed to investigate how chronic intermittent hypoxia (IH), the main pathophysiology of OSA, exacerbates asthma and whether Ang-(1-7) protects against chronic IH-induced airway remodeling in asthma. We exposed ovalbumin (OVA)-challenged asthma mice to chronic IH and observed that chronic IH aggravated airway inflammation and collagen deposit in OVA-challenged mice. Compared with the OVA group, the OVA + chronic IH group had a lower expression level of epithelial marker E-cadherin and higher expression levels of mesenchymal markers α-smooth muscle actin and collagen IV in airway epithelia, accompanied with activation of TGF-ß/Smad pathway. These changes were reversed by the administration of Ang-(1-7). Consistently, Ang-(1-7) mitigated chronic IH-induced activation of TGF-ß-mediated EMT in lipopolysaccharide-treated bronchial epithelial cells in a dose-dependent manner, which was blocked by Ang-(1-7)-specific Mas receptor antagonist A779. Taken together, Ang-(1-7) rescued chronic IH-aggravated TGF-ß-mediated EMT to suppress airway remodeling, implying that RAS activity is involved in the mechanisms of OSA-related airway dysfunction in asthma. SIGNIFICANCE STATEMENT: OSA is a risk factor for refractory asthma. In this study, we aimed to explore the mechanisms of how OSA exacerbates refractory asthma. We found that chronic IH induces TGF-ß-mediated EMT and aggravates airway collagen deposit. We also found that Ang-(1-7) erased the aggravation of TGF-ß-mediated EMT and epithelial fibrosis upon chronic IH exposure. These findings provided new insights that the ACE2/Ang-(1-7)/Mas axis might be considered as a potential therapeutic target for patients with asthma and OSA.

Epigallocatechin-3-gallate enhances tomato resistance to tobacco mosaic virus by modulating RBOH1-dependent H2O2 signaling.

Tobacco mosaic virus (TMV) is one of the most damaging plant viruses from an economic and research point of view. Epigallocatechin-3-Gallate (EGCG), a flavonoid type secondary metabolite can selectively improve plant defense against pathogens; however, the effect of EGCG on plant defense against TMV and the underlying mechanism(s) remain elusive. In this study, exogenous EGCG application increased plant resistance to TMV as revealed by significantly decreased transcript levels of TMV-coat protein (CP) in tomato leaves. A time-course of H2O2 concentrations in tomato leaves showed that TMV inoculation rapidly increased the H2O2 accumulation, reaching its peak at 3 days post-inoculation (dpi) which remained the highest until 6 dpi. However, the combined treatment of EGCG and TMV remarkably decreased the concentrations of H2O2 at 3 and 6 dpi. Meanwhile, the transcript levels of RESPIRATORY BURST OXIDASE HOMOLOG 1 (SlRBOH1) were significantly increased by either EGCG or TMV inoculation, but the EGCG treatment along with TMV caused a further upregulation in the SlRBOH1 transcripts compared with that in only TMV-inoculated plants. Chemical scavenging of H2O2 or silencing SlRBOH1 both compromised the EGCG-induced enhanced resistance to TMV. Furthermore, EGCG-induced elevation in the activity of antioxidant enzymes was abolished by SlRBOH1 silencing, suggesting that EGCG enhanced defense against TMV by increasing the antioxidant enzyme activity via RBOH1-dependent H2O2 signaling. Taken together, our results suggest that EGCG functioned to maintain a delicate balance between ROS signaling and ROS scavenging via RBOH1, which enhanced tomato resistance to TMV.

AMPK/FOXO1 signaling pathway is indispensable in visfatin-regulated myosin heavy chain expression in C2C12 myotubes.

OBJECTIVE: Few studies have addressed the effects of visfatin on skeletal muscle remodeling. The aim of the study was to investigate the effects of visfatin on the expressions of myosin heavy chain (MHC) and its isoforms, the major indicator of fiber types and contractile properties of skeletal muscle. MATERIALS AND METHODS: Levels of MHC, MHC I, MHC IIa, MHC IIb, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), p-AMPK and forkhead box protein O1 (FOXO1) were tested in visfatin-treated C2C12 myotubes. C2C12 myotubes were treated with visfatin combined with AMPK inhibitor or AMPK activator to investigate the role of AMPK in visfatin-mediated MHC expression. FOXO1 was overexpressed or knocked down in C2C12 myotubes to explore the role of FOXO1 in visfatin-mediated MHC expression. RESULTS: Compared with the vehicle group, treatment with 5 µg/ml visfatin increased the levels of total MHC and its isoforms, MHC I, MHC IIa and MHC IIb, by 1.93, 1.84, 1.80, and 1.92 folds, respectively (all p = 0,001). Visfatin suppressed AMPK phosphorylation and decreased FOXO1 expression in C2C12 myotubes. The effects of visfatin on MHC I and MHC IIa expression were canceled by AMPK activator AICAR. FOXO1 overexpression minimized the visfatin-induced upregulation of MHC I, MHC IIa and MHC IIb. The effect of AMPK activator AICAR on MHC and its isoforms expression was minimized by knockdown of FOXO1. CONCLUSIONS: The findings revealed that visfatin promoted expressions of MHC and its isoforms in C2C12 myotubes via suppressing AMPK/FOXO1 signaling pathway.

Emphysema extent on computed tomography is a highly specific index in diagnosing persistent airflow limitation: a real-world study in China.

OBJECTIVE: The diagnostic value of emphysema extent in consistent air flow limitation remains controversial. Therefore, we aimed to assess the value of emphysema extent on computed tomography (CT) on the diagnosis of persistent airflow limitation. Furthermore, we developed a diagnostic criterion for further verification. MATERIALS AND METHODS: We retrospectively enrolled patients who underwent chest CT and lung function test. To be specific, 671 patients were enrolled in the derivation group (Group 1.1), while 479 patients were in the internal validation group (Group 1.2). The percentage of lung volume occupied by low attenuation areas (LAA%) and the percentile of the histogram of attenuation values were calculated. RESULTS: In patients with persistent airflow limitation, the LAA% was higher and the percentile of the histogram of attenuation values was lower, compared with patients without persistent airflow limitation. Using LAA% with a threshold of -950 HU >1.4% as the criterion, the sensitivity was 44.3% and 47.2%, and the specificity was 95.2% and 95.7%, in Group 1.1 and Group 1.2, respectively. The specificity was influenced by the coexistence of interstitial lung disease, pneumothorax, and post-surgery, rather than the coexistence of pneumonia, nodule, or mass. Multivariable models were also developed. CONCLUSION: The emphysema extent on CT is a highly specific marker in the diagnosis of persistent airflow limitation.

Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin.

Diabetic kidney disease (DKD) is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening, mesangial expansion, and glomerular sclerosis, eventually leading to end-stage renal disease. This study aimed to investigate the melioration effect of Codonopisis tangshen Oliv. (COD) on the DKD model, which was established by unilateral nephrectomy (UN)-high fat diet feeding (HFD) combined with streptozotocin (STZ). After the DKD rats were oral treated with COD at a dose of 2.7 mg/kg for 4 consecutive weeks, the blood glucose, lipid metabolism, renal function, inflammatory mediators, and fibrosis-associated proteins were examined. In vivo, the COD administration obviously relieved the weight loss, water intake, and blood glucose; decreased the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels; and improved the renal function by reducing the expression of serum creatinine, uric acid, and urinary protein compared with the model group. The levels of pro-inflammatory cytokines of tumor necrosis factor-α, interleukin-1ß, and IL-6 were significantly inhibited by COD. Meanwhile, the deposition of collagen fiber was markedly increased, and the protein and mRNA expressions of transforming growth factor-ß1 and α-smooth muscle actin were markedly elevated in DKD rats, but they were decreased to some extent after the COD treatment. In conclusion, COD exhibited a protective effect on the UN-HFD feeding combined with STZ-induced DKD model by improving the blood glucose and lipid metabolism, relieving the inflammatory response, and mitigating the renal fibrosis, which provided scientific evidence for its applications in clinic.

Favorable response to pemetrexed, cisplatin and bevacizumab in invasive mucinous adenocarcinoma: A case report and literature review.

Invasive mucinous adenocarcinoma (IMA) was formerly referred to as mucinous bronchioloalveolar carcinoma. The lack of effective chemotherapy and comprehensive treatment for this type of tumor poses a great challenge in clinical practice. We herein report the case of a male patient with IMA who was treated with a combination of pemetrexed (500 mg/m2), cisplatin (75 mg/m2) and bevacizumab (15 mg/kg) as first-line chemotherapy. The patient achieved significant radiological improvement with 6 courses of this regimen. After the tumor progressed, the patient again achieved marked improvement with an additional 4 courses of the same regimen. The patient survived for a total of 30 months after the first chemotherapy. Therefore, bevacizumab in combination with pemetrexed/cisplatin may be an effective strategy for the treatment of IMA. The available literature on this chemotherapy regimen was also reviewed and discussed in the present study.

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner.

BACKGROUND/AIMS: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH) on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK) contributed to metabolic responses to IH in liver cells. METHODS: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour) or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. RESULTS: IH decreased insulin-stimulated protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1) expression and phosphoenolpyruvate carboxykinase (PEPCK) transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3ß phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. CONCLUSION: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3ß phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.