96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients.

Background and Aims: Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results. Methods: Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters. Results: Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (p=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend. Conclusions: TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).

JAK/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK - Anaplastic Large Cell Lymphomas : New Insights into Their Heterogeneity.

Systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a group of heterogenous CD30 + T-cell non-Hodgkin lymphomas. Previous studies have highlighted the importance of JAK/STAT3 signaling activation in the molecular pathogenesis of ALK - ALCLs. In the present study, we aimed to establish a potential relationship between JAK/STAT3 signaling activation and clinicopathologic features in ALK - ALCLs, and further recognize the heterogenous nature of these neoplasms. Immunohistochemistry staining of the phosphorylated-STAT3 (p-STAT3) and dual-specificity protein phosphatase 22 ( DUSP22 ) gene rearrangement analysis were performed. Forty-five cases of ALK - ALCL were divided into 3 groups, including 9 DUSP22 -rearranged ALCLs, 21 p-STAT3 + double-negative (DN) ALCLs (both ALK and DUSP22 rearrangement negative), and 15 p-STAT3 - DN-ALCLs. Morphologically, p-STAT3 + DN-ALCLs exhibited sheet-like neoplastic cells and sometimes showed large pleomorphic cells scattered in a lymphocyte-rich background more frequently than those in other ALK - ALCLs subtypes. Phenotypically, the p-STAT3 + DN-ALCLs frequently expressed cytotoxic molecules, epithelial membrane antigen, and programmed death-ligand 1, whereas CD3 and CD5 expression was not observed. Clinically, patients with p-STAT3 + DN-ALCLs had a better prognosis than those with p-STAT3 - DN-ALCLs. These observations suggest that p-STAT3 + DN-ALCLs represent a distinct subtype of ALK - ALCLs. Identifying ALK - ALCL subtypes by using p-STAT3 staining and DUSP22 rearrangement is a promising approach that may contribute to risk stratification and better treatment decisions in the future clinical practice.

Efficacy and safety analysis of high-flow nasal cannula in children with bronchiolitis: a systematic review and meta-analysis.

Background: Oxygen therapy is one of the most common treatments for bronchiolitis, But traditional standard oxygen therapy is poorly tolerated by patients. Nasal continuous positive airway pressure (nCPAP) also has many contraindications. High-flow nasal cannula (HFNC), as a new method of adjunctive respiratory support, has received extensive attention in oxygen therapy in pediatric. In this meta-analysis, we evaluated the efficacy and safety of HFNC in the treatment of infant bronchiolitis. Methods: We searched PubMed, Web of Science, CNKI, GeenMedical, Wanfang, and Weipu using the following keywords: children with respiratory diseases, infant bronchiolitis, bronchiolitis treatment, HFNCs, warming and humidifying high-flow, nasal catheter oxygen inhalation, and conventional oxygen therapy. The publication time was set from the establishment of the database to October 2021. Selected articles were randomized controlled trial (RCT) studies in which the patients were less than 16 years old and the experimental group was treated with HFNCs, and the control group was treated with nCPAP or conventional oxygen. After extracting the data, the study subjects were divided into HFNC treatment and control groups. The Cochrane risk of bias tool was used to assess the quality of the included literature, and RevMan 5.30 was used for meta-analysis. Results: Seven articles met the inclusion criteria. All articles described random sequence generation, four articles reported on allocation concealment, only two articles reported on the double-blind method. All articles described the complete blinding of outcome evaluation bias, outcome data bias, selective reporting bias, and other risk biases. The HFNC treatment group included 436 children, 405 children treated with nCPAP or standard oxygen therapy were included in the control. The results showed that the failure rate [relative risk (RR) is 0.57, 95% CI: 0.43-0.76], respiratory rate [mean difference (MD) is -7.43, 95% CI: -8.42 to -6.43], and social function (MD is 0.76, 95% CI: -0.32 to 1.83) of HFNC-treated children with bronchiolitis were significantly different to that of the control group patients. Discussion: HFNC treatment provides the same improvement in arterial oxygen partial pressure as standard oxygen therapy or transnasal positive airway pressure treatment, but it is significantly better at improving the respiratory rate of children with bronchiolitis.

Hydrogen Attenuates Thyroid Hormone-Induced Cardiac Hypertrophy in Rats by regulating angiotensin II type 1 receptor and NADPH oxidase 2 mediated oxidative stress.

Cardiac hypertrophy occurs as a result of high levels of thyroid hormone, which may contribute to heart failure and is closely related to oxidative stress. Hydrogen is a good antioxidant. In this study, we found that intragastric levothyroxine administration for two weeks caused obvious cardiac hypertrophy without reduced systolic function. Additionally, hydrogen inhalation ameliorated the levothyroxine-induced metabolic increase and cardiac hypertrophy in rats. Serum brain natriuretic peptide expression was also attenuated by hydrogen treatment. However, hydrogen had no significant effect on levothyroxine -induced serum troponin I and serum thyroid hormone changes. Hydrogen treatment also reduced the levothyroxine-induced increase in cardiac malondialdehyde, 8-hydroxy-2-deoxyguanosine and serum hydrogen peroxide levels and upregulated superoxide dismutase and glutathione peroxidase activity. Additionally, western blotting results showed that hydrogen inhalation inhibited the expression of cardiac nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), angiotensin II type 1 receptor, sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospho-phospholamban and α-myosin heavy chain proteins. In conclusion, the present study revealed a protective effect of hydrogen on levothyroxine -induced cardiac hypertrophy by regulating angiotensin II type 1 receptors and NOX2-mediated oxidative stress in rats.

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B.

BACKGROUND: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS: We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION: TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

Secretory carcinoma of the breast with multiple distant metastases in the brain and unfavorable prognosis: a case report and literature review.

BACKGROUND: Secretory carcinoma of the breast is one of the rarest entities, accounting for less than 0.15 % of all infiltrating breast carcinomas. It has characteristic histopathological and molecular features and, in general, a more favorable prognosis. In this case report, we describe a local, advanced secretory carcinoma of the breast with aggressive course and an unfavorable outcome. CASE PRESENTATION: A hard, painless, and palpably bossed mass approximately 12.0 cm in diameter occupied most of the left breast of a 39-year-old woman with fixation to the overlying skin. Breast ultrasonography and magnetic resonance imaging (MRI) scans gave the same grading as BI-RADS IV. A needle biopsy was performed, and the pathological diagnosis was secretory carcinoma. Neoadjuvant chemotherapy (NAC) was then performed, after which ultrasonography and MRI scans revealed chemo-resistance of the tumor to NAC. Left breast mastectomy and axillary lymphadenectomy were subsequently performed. Tumor cells were triple-negative and positive for S-100 and periodic acid-Schiff (PAS) staining. Fluorescence in-situ hybridization (FISH) analysis indicated a fusion arrangement of the ETV6-NTRK3 gene. The patient developed multiple distant metastases in the brain and died of these metastases 19 months after initial diagnosis. CONCLUSIONS: Secretory carcinomas of the breast have been described as a low-grade histologic subtype with a favorable prognosis. This case showed chemo-resistance to neoadjuvant chemotherapy, multiple distant metastases, and a final unfavorable outcome. Further research is needed to better understand the behavior and treatment of this rare tumor.

The correlation between neonatal vitamin D levels and the risk of childhood asthma attacks.

BACKGROUND: To explore the correlation between neonatal vitamin D levels and the risk of asthma in children aged 3-9 years. METHODS: A total of 1,534 subjects were selected, and clinical and laboratory test data of all subjects were collected at birth, including 25-hydroxyvitamin D3 [25(OH)D3] levels, gender, season of birth, birth weight; whether delivery was premature, cesarean section, or primipara; and parental details including maternal age, ethnicity, level of education, history of smoking, and history of maternal or paternal asthma. The level of 25(OH)D3 was used as a continuous variable to analyze its correlation with the risk of asthma using the Cox proportional regression model. In addition, subjects were divided into four groups according to their 25(OH)D3 quartiles, and the first quantile group was used as a reference to analyze the risk of asthma in the other groups. Further subgroup analysis was conducted according to the patients' gender and birth season. RESULTS: Among the 1,534 subjects included, there were 107 cases in the asthma-affected group and 1,427 cases in the normal control group. Compared with the control group, the level of 25(OH)D3 in the asthma group was significantly lower (P=0.03), the mother's education level was lower (P=0.002), but the preterm birth rate, cesarean section rate, and parental asthma prevalence rate were significantly higher (all P<0.05). When the neonatal 25(OH)D3 was divided into quartiles to perform a categorical variable analysis, we found that compared with the first quantile (Q1, 0.0-25.1 mmol/L), the risk of asthma in Q4 was reduced by 50% (HR=0.50, 95% CI: 0.38-0.76). The second quantile group (Q2) and the third quantile group (Q3) showed no significant difference in the risk of disease compared with Q1 but showed a trend of decreasing risk as the quantile group increased (the trend P values were both <0.05). This correlation was still valid when a stratified analysis was made based on gender and birth season. CONCLUSIONS: There is a significant correlation between a reduced vitamin D level in newborns and the subsequent risk of asthma in children aged 3-9 years. Moreover, the level of vitamin D is an independent risk factor for childhood asthma.

Clinicopathological characterization of follicular helper T-cell-derived peripheral T-cell lymphoma involving Waldeyer's ring.

Follicular helper T-cell-derived peripheral T-cell lymphoma (TFH-derived PTCL) initially present in the Waldeyer's ring is a rare condition with a challenging diagnosis. This study aimed to evaluate the clinicopathological characteristics and diagnosis of Waldeyer's ring TFH-derived PTCL and raise awareness of this type of lymphoma. A series of 13 cases of Waldeyer's ring TFH-derived PTCL were retrospectively analyzed. Clinically, most patients presented with localized manifestations, such as painless cervical lymphadenopathy (7/13), pharyngalgia (6/13), and nasal obstruction (3/13), and systemic symptoms were uncommon. Macroscopically, plump mass (9/13) and nodular lesions (3/13) covered with intact and tense mucosa were the main findings on fiberoptic laryngoscopy examination. Pathologically, diffuse infiltration with atypical lymphocytes in the lamina propria (10/13) was the most common growth pattern. Clear cells (9/13) and vascular proliferation (11/13) within a polymorphic inflammatory background (11/13) were frequently observed. All cases expressed at least two TFH markers: PD-1 in 92.3% (12/13), BCL6 in 69.2% (9/13), CXCL13 in 53.8% (7/13), and CD10 in 46% (6/13). Targeted next-generation sequencing analysis identified frequent mutations, including TET2 (10/11), RHOA (6/11), DNMT3A (3/11), and IDH2 (2/11). The overall survival rate at 2 years was 35.5%, and survival analysis revealed that patients with localized disease showed better overall survival (P = 0.022). In conclusion, careful morphological observation combined with immunohistochemistry and molecular analysis would help in diagnosis of TFH-derived PTCL involving the Waldeyer's ring, which is a rare condition that frequently presents with atypical clinical manifestations.

Molecular profiling of Chinese systemic anaplastic large cell lymphoma patients: novel evidence of genetic heterogeneity.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is a rare non-Hodgkin lymphoma. A comprehensive understanding of the genetic and clinical heterogeneity of ALCL may help to improve the clinical management of patients with ALCL. However, due to the rarity of the disease, the genetic heterogeneity of ALCL has not been well elucidated. This study aimed to comprehensively elucidate the mutational landscape of tumor tissue samples from patients with systemic ALCL. METHODS: Thirty-six patients with systemic ALCL were enrolled in this retrospective study. Immunohistochemistry (IHC) was performed on tumor tissues at baseline to identify anaplastic lymphoma kinase (ALK) fusions. Capture-based targeted next-generation sequencing (NGS) with a panel spanning 112 lymphoma-related genes, including ALK rearrangements, was also performed on tumor tissue samples. RESULTS: A total of 102 mutations were identified in the entire cohort. Among the 36 patients included in this analysis, 14 (38.8%) were ALK positive, as determined by IHC, while NGS showed 12 patients (33.3%) to harbor ALK rearrangements. Younger patients were more likely to have ALK-positive ALCL (P=0.011). Patients with wild-type (WT) ALK were more likely to have single-nucleotide variants (SNVs) and insertions or deletions (INDELs) than patients with ALK rearrangements (P=0.027). Among the 22 patients with WT ALK, the most commonly mutated genes were TP53 (n=6, 27.3%), followed by NOTCH1 (n=5, 22.7%), KMT2D (n=3, 13.6%), KRAS (n=3, 13.6%), TET2 (n=3, 13.6%), and JAK1 (n=2, 9.1%). Mutations in PRDM1, a commonly mutated gene in ALK-negative patients, were not detected in our ALK-negative cohort. Start-loss of beta-2-microglobulin (B2M) was detected in another patient; this patient had a favorable prognosis, with an overall survival exceeding 19 months. CONCLUSIONS: Our study revealed the unique genomic profiles of Chinese ALCL patients and represents an incremental step in deepening the understanding of the genetic heterogeneity of ALCL patients.

Rian/miR-210-3p/Nfkb1 Feedback Loop Promotes Hypoxia-Induced Cell Apoptosis in Myocardial Infarction Through Deactivating the PI3K/Akt Signaling Pathway.

Myocardial infarction (MI) is a severe disease that could lead to reversible or irreversible ischemic heart damage. A previous study has revealed that microRNA mmu-miR-210-3p expression is downregulated in fat-1 transgenic mice post-MI. Nevertheless, the specific mechanism of miR-210-3p in MI remains obscure. In this study, we observed that miR-210-3p expression was downregulated in the mice's left ventricle post-MI, and miR-210-3p expression was suppressed while cell apoptosis was promoted in H9c2 cells under hypoxia condition. Besides, miR-210-3p overexpression could enhance cell proliferation and inhibit cell apoptosis in hypoxia-treated H9c2 cells. Then, molecular mechanism assays revealed that miR-210-3p overexpression could activate the PI3K/Akt pathway, and nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1) was the target of miR-210-3p. In addition, RNA imprinted and accumulated in nucleus (Rian), a long noncoding RNA, could sponge miR-210-3p to upregulate Nfkb1 expression. Besides, Nfkb1 was verified to facilitate the transcription of Rian by binding with a Rian promoter. Furthermore, rescue assays revealed that both Nfkb1 and PI3K/Akt pathway are engaged in the Rian-mediated cell proliferation and apoptosis in hypoxia-treated H9c2 cells. In conclusion, a Rian/miR-210-3p/Nfkb1 feedback loop enhances hypoxia-induced cell apoptosis in MI through deactivating the PI3K/Akt pathway.

[Dynamic Changes in Hydrochemical Characteristics and Influencing Factors in the Karst Watershed Flood Process].

The hydrochemistry of river water in a karst basin has a rapid response to the rainstorm/flood process, which is an important process of the karst carbon cycle and should not be ignored. Based on the dynamic monitoring of the hydrochemical characteristics of the flood process in the Yangshuo section on November 8-12, 2015, the dynamic change in the main ions and the influencing factors were analyzed, and the concentration and flux of inorganic carbon from different sources were calculated. The results showed that the hydrochemistry types in different stages of the flood area belonged to the Ca-HCO3 type. The ions were mainly sourced from carbonate weathering, and affected by silicate weathering, rainfall, and human activities. Because of the hydrological process, the weathering strength of carbonate rocks sharply weakened at the beginning of the flood, and then gradually increased. The concentrations of HCO3-, Ca2+, and Mg2+ sharply decreased at the beginning of the flood, then gradually increased, and continued to increase in the second flood process because of the waterlogging in the karst system. Because of the waterlogging, the reaction time between water and rock become longer; thus, the concentrations are higher. The dynamic changes in SO42-, Cl-, Na+, and K+ were mainly affected by precipitation and human activities. At the beginning of the flood, the concentrations of SO42-, Cl-, Na+, and K+ increased because the runoff takes more ions sourced from activities. The concentrations of SO42-, Cl-, Na+, and K+ decreased with the decrease of easily transported substances. At the lowest point of concentration, SO42- and Cl- were mainly sourced from precipitation, and Na+ and K+ were mainly sourced from precipitation and silicate weathering. The weathering of carbonates by carbonic acid was the main source of inorganic carbon, accounting for 74.3% of total inorganic carbon on average. Because of the input of sulfuric/nitric acid, the contribution of the weathering of carbonates by sulfuric/nitric acid to the inorganic carbon cannot be ignored, and the contribution increased significantly in the flood, up to 31.7%. The geological carbon sinks before the flood, and during the first and second flood processes in the Yangshuo section were 1.28×108, 5.28×108, and 11.52×108 g·d-1, respectively. The geological carbon sink before the flood was equal to the annual average flux, whereas the geological carbon sink in the flood process was several times that of the annual average flux. Moreover, because of the significant difference in the weathering strength of carbonate rocks during the two floods, there was also a significant difference in the amount of geological carbon sink under the same discharge.

Effects of radiofrequency ablation combined with transarterial chemoembolization and antiviral therapy on the prognosis and quality of life in primary chronic HBV-related liver cancer.

PURPOSE: To investigate the effects of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) and antiviral therapy on the prognosis and quality of life in primary chronic hepatitis B virus (HBV)-related liver cancer. METHODS: A total of 80 hepatitis B patients complicated with hepatocellular carcinoma treated in our hospital from March 2016 to February 2018 were selected and divided into the control group (n=40) and the observation group (n=40) using a random number table. The patients in the control group were treated with RFA combined with TACE, while those in the observation group were additionally treated with entecavir. The HBV-DNA load and alpha fetoprotein (AFP) level during intervention and the liver function before and after intervention were compared between the two groups. The patients were followed up for 2 years after treatment, the clinical therapeutic effects in both groups were recorded, and the correlations of HBV-DNA load, AFP level and alanine aminotransferase (ALT) level with the survival time of patients were analyzed. RESULTS: At 1 and 3 months after intervention, the HBV-DNA load in the observation group was significantly lower than that before intervention (p<0.05), and it was also significantly lower than in the control group (p<0.05). At 1 and 3 months after intervention, the AFP level was lowered in both groups compared with that before the intervention (p<0.05), and it was also lower in the observation group than in the control group (p<0.05). After intervention, the levels of total bilirubin (Tbil), aspartate aminotransferase (AST) and ALT in the observation group were lower than those before the intervention (p<0.05), and they were also lower than those in the control group (p<0.05). Moreover, the disease progression in the observation group was significantly lower than in the control group, and the 1-year and 2-year survival in the observation group was longer compared with the control group. The HBV-DNA load, AFP level and ALT level were negatively correlated with the survival of patients (p<0.05). CONCLUSIONS: The RFA combined with TACE and regular antiviral therapy for HBV-related liver cancer is of significance in reducing the HBV-DNA load and tumor markers, improving the liver function, promoting the overall clinical therapeutic effect and prolonging the survival of patients.

TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib.

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment. We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement NSCLC. METHODS: Sixty-six ALK rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. TP53 mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: TP53 mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 65 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between TP53 gene wild group and mutation group patients (P=0.038, P=0.021, respectively). CONCLUSIONS: TP53 mutations reduce responsiveness to crizotinib and worsen prognosis in ALK rearrangement NSCLC patients.

Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway.

In the recent years, increasing evidences identify circular RNAs (circRNAs) as a class of important regulators in various human cancers. Nevertheless, the functions and mechanisms of most circRNAs in cancer cells remain largely unknown. In this study, we found out a significantly downregulated circRNA circC3P1 in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. And our results indicated that circC3P1 expression level was negatively correlated with TNM stage, tumor size and vascular invasion in HCC. Moreover, we found that circC3P1 overexpression dramatically inhibited the proliferation, migration and invasion of HCC cells in vitro and in vivo. In terms of mechanism, we found that circC3P1 could promote PCK1 expression through sponging miR-4641 in HCC cells. We showed that miR-4641 expression was negatively correlated with that of either circC3P1 or PCK1 in HCC tissues. Finally, by functional experiments, we demonstrated that knockdown of PCK1 significantly attenuated the effects of circC3P1 overexpression on HCC cell proliferation, migration and invasion. In summary, our findings illustrated that circC3P1 acts as a tumor suppressor via enhancing PCK1 expression by sponging miR-4641 in HCC.

Maslinic acid protects against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.

Acute liver injury is a life-threatening syndrome that often caused by hepatocyte damage. In this study, we investigated the protective effects of maslinic acid (MA) on lipopolysaccharide (LPS)/d-galactosamine (D-gal)-induced acute liver injury and clarified its mechanism. Mice acute liver injury model was induced by given LPS and D-gal and MA was given intraperitoneally 1 h before LPS and D-gal. Our results showed that MA protected against liver injury by attenuating liver histopathologic changes, serum AST and ALT levels. The increased inflammatory cytokines TNF-α and IL-6 in serum and liver tissues were also inhibited by MA. The level of MDA and the activity of MPO in liver tissues were up-regulated by LPS/D-gal and dose-dependently inhibited by MA. Furthermore, MA attenuated hepatic NF-κB protein expression and increased hepatic Nrf2 and HO-1 protein expression. Taken together, MA offers a protective role against LPS/D-gal-induced liver injury through suppressing NF-κB and activating Nrf2 signaling pathways.

Simultaneous VENTANA IHC and RT-PCR testing of ALK status in Chinese non-small cell lung cancer patients and response to crizotinib.

BACKGROUND: ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements. METHODS: A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent. RESULTS: Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion. CONCLUSIONS: VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib.

The GF-3 SAR Data Processor.

The Gaofen-3 (GF-3) data processor was developed as a workstation-based GF-3 synthetic aperture radar (SAR) data processing system. The processor consists of two vital subsystems of the GF-3 ground segment, which are referred to as data ingesting subsystem (DIS) and product generation subsystem (PGS). The primary purpose of DIS is to record and catalogue GF-3 raw data with a transferring format, and PGS is to produce slant range or geocoded imagery from the signal data. This paper presents a brief introduction of the GF-3 data processor, including descriptions of the system architecture, the processing algorithms and its output format.

Patients harboring ALK rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report.

Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression. Then, next-generation sequencing (NGS) was carried out and detected a TP53 gene mutation, an ALK rearrangement, and no loss of the retinoblastoma gene (RB). Although a regimen for small-cell lung cancer may be one treatment option, a heterogeneous tumor may exist at the time of diagnosis and manifest during the course of disease.