Prevalence, characteristics, evaluation, and management of carotid body tumors: Systematic analysis based on available evidence.

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.

Meta-analysis of proton pump inhibitor use and the risk of developing gastric cancer or colorectal cancer.

To evaluate the relationship between the use of proton pump inhibitors (PPI) and the risk of gastric cancer and colorectal cancer by using meta-analysis. Computer search PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang database to obtain relevant literature on the use of PPI and the risk of gastric cancer and colorectal cancer, extract relevant data, and use Stata14.0 for Meta-analysis. A total of 24 articles were included, including 12 articles for gastric cancer and 12 articles for colorectal cancer. A total of 5 313 749 persons were included in the study and analysis. Meta-analysis results showed that the risk of gastric cancer in PPI users was significantly increased [risk ratio (RR) = 2.04, 95% confidence interval (CI) (1.33-2.75)], and the regional subgroup analysis results showed that in Europe [RR = 2.01, 95% CI (0.92, 3.09), P < 0.05] and Asia [RR = 2.15, 95% CI (1.16, 3.14), P < 0.05] This risk is higher, and Asia is higher than Europe. The risk of colorectal cancer is slightly increased [RR = 1. 22, 95% CI (1.03, 1.40, P < 0.05], and the regional subgroup analysis results show that in Europe [RR = 1.05 95% CI (0.98, 1.12), P < 0.05] and Asia [RR = 1.18, 95% CI (1.10, 1.27), P < 0.05]. This risk is low, but Asia is higher than Europe. The use of PPI significantly increases gastric cancer However, the risk of colorectal cancer is not significantly increased. The risk of gastric cancer and colorectal cancer in the population using PPI in Asia is higher than that in Europe.

Treatment-related gastrointestinal adverse events of nivolumab plus ipilimumab in randomized clinical trials: a systematic review and meta-analysis.

The authors used a meta-analysis to evaluate the risks of gastrointestinal adverse events in the cotreatment of malignant tumors with nivolumab and ipilimumab. The meta-analysis revealed that the most common gastrointestinal adverse event at all grades was diarrhea, followed by nausea, decreased appetite, vomiting, constipation, colitis and abdominal pain. The most common severe gastrointestinal adverse events were colitis and diarrhea. Different administration schemes differ in the risk of such events, and thus these events may be minimized by modulating the administration scheme of the cotreatment.

Improved bone and renal safety in younger tenofovir disoproxil fumarate experienced chronic hepatitis B patients after switching to tenofovir alafenamide or entecavir.

INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.

Different effects of continuous and pulsed Benzo[a]pyrene exposure on metabolism and antioxidant defense of large yellow croaker: Depend on exposure duration.

This study aims to compare differential effects of continuous and pulsed BaP exposures on metabolism and antioxidant defense in the liver of large yellow croaker. Fish were subjected to BaP for 4 days and 36 days in three exposure regimes with the same time-averaged concentration of BaP: 4 µg/L BaP continuously, 8 µg/L BaP for 24 h every other day or 16 µg/L BaP for 24 h every 4 days. Our results showed that compared to pulsed BaP exposures, continuous BaP exposure reduced BaP metabolism (CYP1A, CYP3A and AHR transcriptional expressions, GSH content, GSH/GSSG ratio, EROD and GST activities) and antioxidant defense (T-SOD activity) on day 4, resulting to the increases in MDA and PC contents, indicating that continuous BaP exposure induced more severe oxidative damage during the early stage of exposure. But continuous BaP exposure reduced MDA and PC contents by improving BaP metabolism and antioxidant defense during the late stage of exposure. CYP1B transcriptional expression and CAT activity were unsuitable biomarkers of both continuous and pulsed BaP exposures. In conclusion, our results demonstrated differential effects of continuous and pulsed exposures on BaP metabolism and antioxidant responses, which were depend on exposure duration.

Different cold tolerances among three strains of large yellow croaker: related to antioxidant defense and energy metabolism.

The aim of this study was to compare low-temperature tolerances in different strains of large yellow croaker. Dai Qu (DQ), Min-Yue Dong (MY), and Quan Zhou (NZ) strains of large yellow croaker were subjected to cold stress (8.6 °C) for 12 h, 24 h, 48 h, and 96 h. Survival rate, histological observation, and antioxidant and energy metabolism indicators were determined. The results showed that compared with the DQ group and MY group, NZ group aggravated hepatic structure, enhanced ROS, lactate, and anaerobic metabolism (PK gene expression and activity), while inhibited ATP, GSH, antioxidant enzymes (mRNA levels and activities of SOD, GPx, and CAT), and aerobic metabolism enzymes (mRNA levels and activities of F-ATPase, SDH, and MDH), indicating the reduction of cold tolerance in the NZ group was closely correlated with the decrement of antioxidative capacity and energy metabolism efficiency. Nrf2 and AMPK gene expressions were correlated with antioxidant and energy metabolism mRNA levels, respectively, suggesting Nrf2 and AMPK might participate in the modulation of target genes during the cold-stress adaptation. In conclusion, low temperature tolerance of fish depended on the antioxidant defense and energy metabolism efficiency, which contributes to understanding the underlying mechanisms of cold adaptation in large yellow croaker.

The characteristics of carotid body tumors in high-altitude region: Analysis from a single center.

OBJECTIVES: Though carotid body tumors are rare, increasing attentions have been given because of malignant transformation and high surgical risk. However, at present, the characteristics and etiology still remain unclear. Our study was designed to describe the clinical features of carotid body tumors in our institution and to compare the results with previous reports. METHODS: We retrospectively reviewed carotid body tumor patients diagnosed in our institution from January 2015 to May 2020. The demographics, comorbidities, lesion location, anatomic characteristics, complications, and postoperative outcomes were evaluated. Carotid body tumor measurements were determined from computed tomography, magnetic resonance imaging, and carotid arteriography examination. We described and compared the clinical features of carotid body tumors in our institution and other reports. RESULTS: We totally identified 122 carotid body tumor cases for the present analysis. The mean age was 50.26 years, with the majority being female (82%). The commonest presentation was a painless neck mass (68%). For the distribution of nationality, most patients were the Han nationality (69.7%). The mean altitude of habitat of patients was 2689.4 km; 19.7% patients suffered bilateral lesions. The main blood supply of carotid body tumors was from external carotid artery (54.1%). For patients who received operation, 11 (11.2%) patients experienced cranial nerve injury. The maximal diameter of tumors was 3.99 ± 1.98 cm in male and 3.38 ± 1.36 cm in female. The volume of tumors was 31.49 ± 29.76 cm3 in male and 15.27 ± 13.06 cm3 in female. The distance to base of skull of tumors was 3.39 ± 1.07 cm (3.99 ± 1.98 cm in male vs 3.38 ± 1.36 cm, P < 0.05). Two patients (2.04%) were identified as having malignant carotid body tumor. CONCLUSIONS: Though carotid body tumor had a low morbidity and multitudinous clinicopathologic features, it was apt to middle-aged women and the main blood supply was from external carotid artery. The painless neck mass was the commonest presentation of carotid body tumors. There were significant difference between male and female patients regarding platelet, hemoglobin, distance to base of skull, tumor volume, altitude of habitat, carotid body tumor location, and hypertension.

Effect of temperature on synthesis of clavulanic acid and impurity substance G during fermentation by Streptomyces clavuligerus.

Effect of temperature on synthesis of Clavulanic acid (CA) and impurity substance G during fermentation by Streptomyces clavuligerus were investigated. Results show that fermentation at 24 °C is the most favorable for CA synthesis though the fermentation duration was 20-30 hours longer than fermentation at 26 and 28 °C. Meanwhile, the impurity substance G was only 110 mg/L in the end broth of fermentation at 24 °C, which was significantly lower than 148 and 180 mg/L of fermentation at 26 and 28 °C, respectively. Correlation of specific growth rate and CA synthesis was statistically analyzed based on data of 10 batches of industrial fermentation. Two temperature-shift strategies were investigated in 50 L fermenter. Fermentation with 26-24 °C temperature strategy achieved 5097 mg/L CA titer, meanwhile the fermentation duration was shortened 24 hours comparing with fermentation at constant 24 °C. Fermentation with 26-24 °C control strategy was validated in a 60 m3 industrial fermenter, in which 4960 mg/L of CA was achieved while impurity G substance was decreased to titer 65 mg/L from 200 to 300 mg/L of normal production.

Optimal drug administration manner would rescue partial virological response in chronic hepatitis B patients with entecavir or tenofovir treatment.

Not all treatment-naïve patients receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy can achieve complete virological response, and many factors may be related with the outcome of partial virological response. This study aimed to determine whether the manner of drug administration affects the antiviral efficacy of ETV/TDF monotherapy. All eligible patients were divided into complete or partial response cohorts based on their virological response following 24-week therapy. Factors related with partial response were evaluated. Patients with partial response were further grouped depending on whether they later adjusted the manner of drug administration, and the antiviral efficacy was compared between the two groups during prolonged treatment. A total of 518 patients were enrolled. Suboptimal drug administration (OR 77.511, P = .000), positive-HBeAg (OR 3.191, P = .000) and ETV treatment (OR 2.537, P = .001) were identified as independent risk factors for partial response. Among patients with partial response, 213 were in the adjusted group and 76 were in the unadjusted group. The percentages of patients with undetectable serum HBV DNA (78.9% vs 31.6%, P < .001) and with normal alanine aminotransferase (ALT) (88.7% vs 68.4%, P < .001) were both higher in the adjusted group than that in unadjusted group following a further 6-month therapy. In conclusion, the manner of drug administration is an important factor influencing the efficacy of ETV/TDF therapy, and optimal drug administration manner can help to increase antiviral efficacy and rescue patients with partial response.

Tenofovir monotherapy versus tenofovir plus entecavir combination therapy in HBeAg-positive chronic hepatitis patients with partial virological response to entecavir.

AIMS: The aim of this retrospective study was to compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy and TDF + entecavir (ETV) combination therapy for chronic hepatitis B (CHB) patients with the partial virological response (PVR) to ETV. METHODS: CHB patients with PVR to ETV were switched to TDF monotherapy or TDF + ETV combination therapy. The primary efficacy outcome was a virological response (VR), and the secondary efficacy outcomes were hepatitis B e antigen (HBeAg) seroconversion and alanine aminotransferase (ALT) normalization. The primary safety outcomes were changes in serum creatinine and serum phosphorus levels. RESULTS: A total of 143 patients were investigated, including 63 patients in the TDF monotherapy group and 80 patients in the TDF + ETV combination therapy group. Baseline demographics and clinical characteristics were comparable between groups. The median age of patients was 44.5 years, and 76.2% of them were male. The VR rate in TDF + ETV group was higher than that of the TDF group at 48 weeks (88.8% vs 71.4%; P = .009). At 48 weeks, the HBeAg seroconversion rate of TDF + ETV group was higher than that of the TDF group (30% vs 15.9%; P = .049). There was no significant difference in the proportion of patients with elevated ALT in the TDF group and TDF + ETV group at 48 weeks (9.5% vs 7.5%; P = .665). After adjusting the treatment regimen, serum creatinine levels increased slightly and serum phosphorus level decreased slightly in both groups. CONCLUSIONS: TDF + ETV combination therapy for 48 weeks had a higher VR rate than TDF monotherapy in CHB patients with PVR to ETV.

Novosphingobium silvae sp. nov., isolated from subtropical forest soil.

A novel bacterial strain, designated FGD1T, was isolated from subtropical forest soil of the Nanling National Forest Park located in Guangdong Province, P.R. China. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain FGD1T was most closely related to Novosphingobium lindaniclasticum DSM 25049T (98.8 %), followed by N. barchaimii DSM 25411T (98.7 %), N. guangzhouense DSM 32207T (98.2 %), N. panipatense DSM 22890T (98.1 %) and other species of Novosphingobium (<98 %). The draft genome sequence was 4.58 Mb in length with a G+C content of 65.1 mol%. The calculated average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain FGD1T and closely related type strains were 77.7‒79.6 % and 21.7-22.9 %, respectively. Major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C14 : 0 2-OH and C16 : 0. The predominant respiratory quinone was ubiquinone 10 and the major polyamine was spermidine. Polar lipids were composed of sphingoglycolipid, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, diphosphatidylglycerol, an unidentified phospholipid and lipid. The polyphasic taxonomic results indicated that strain FGD1T represents a novel species of the genus Novosphingobium, for which the name Novosphingobium silvae sp. nov. is proposed. The type strain is FGD1T (=GDMCC 1.1761T=KACC 21283T).

Discovery of susceptibility loci associated with tuberculosis in Han Chinese.

Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population.

Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotype 6 in Southwest China: Real-world experience of a retrospective study.

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017. Our study screened 130 treatment-naïve patients with chronic HCV GT6 and without liver cirrhosis. A total of 60 HCV GT6 patients were ultimately enrolled. All patients received SOF-based DAAs therapy, including SOF 400 mg plus daclatasvir (DCV) 60 mg daily or SOF 400 mg plus velpatasvir (VEL) 100 mg daily for 12 weeks. The sustained virological response 12 weeks after treatment (SVR12) was 100% (60/60) in treatment-naïve patients with HCV GT6, including 100% (37/37) of patients receiving SOF plus DCV therapy and 100% (23/23) of patients receiving SOF plus VEL therapy. Measurements of liver stiffness were significantly decreased in patients at week 12 (P = 0.014) and week 24 (P < 0.001) of DAAs treatment compared to baseline values. The serum biomarker aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score were also significantly reduced at week 12 and week 24 compared to before treatment (both P < 0.001). SOF-based therapy was well-tolerated, and no serious adverse events were reported. In conclusion, SOF plus DCV and SOF plus VEL were safe and achieved a high SVR12 rate for treatment-naïve patients with HCV GT6 without liver cirrhosis.

Ramlibacter humi sp. nov., isolated from tropical forest soil.

A Gram-stain-negative, aerobic and non-motile strain, designated 18x22-1T, was isolated from a forest soil sample collected from Limushan Nature Reserve in Hainan Province, PR China. Growth occurred at 15-37 °C and pH 6.0-8.0 without NaCl. The 16S rRNA gene sequence analyses showed that strain 18x22-1T was closely related to Ramlibacter tataouinensis DSM 14655T (98.5 %), followed by Ramlibacter henchirensis DSM 14656T (97.9 %) and other Ramlibacter species and formed a stable cluster with R. tataouinensis DSM 14655T, R. henchirensis DSM 14656T, Ramlibacter solisilvae JCM 19319T and Ramlibacter rhizophilus CCTCC AB 2015357T. Results of chemotaxonomic analyses showed that ubiquinone-8 (Q-8) was the major respiratory quinone, and the major fatty acids (>10 % of the total amounts) were C16 : 0 and C17 : 0cyclo. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified aminopholipids and four unidentified phospholipids. The draft genome sequence was 4.47 Mb long with a G+C content of 68.9 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain 18x22-1T and four closely related type strains were in the range of 79.3-82.3 % and 21.9-25.1 %, respectively. The results of phenotypic, phylogenetic and chemotaxonomic analyses supported that strain 18x22-1T represents a novel species of the genus Ramlibacter, for which the name Ramlibacterhumi sp. nov. is proposed. The type strain is 18x22-1T (=GDMCC 1.1584T=KCTC 52922T).

Sphingomonas lenta sp. nov., a slowly growing bacterium isolated from an abandoned lead-zinc mine.

A novel slowly growing member of the genus Sphingomonas, designated 1PNM-20T, was isolated from an abandoned lead-zinc mine in Meizhou, Guangdong Province, PR China. A polyphasic taxonomic study was performed to characterize the novel strain. Growth occurred on Reasoner's 2A (R2A) agar and peptone-yeast extract (PYE) agar, but not in liquid R2A or PYE media. Cells were Gram-stain-negative, aerobic, non-spore-forming, rod-shaped and motile with a polar flagellum (monotrichous). 16S rRNA gene sequence comparison showed that it shared the highest similarity with Sphingomonas carriPR0302T (97.2 %), followed by Sphingomonas spermidinifaciens 9NM-10T (97.0 %), Sphingomonas floccifaciens FQM01T (97.0 %) and other species of Sphingomonas (<97 %). Phylogenetic analyses clearly showed that strain 1PNM-20T fell into the cluster of Sphingomonas, and was most closely related to S. carri. The draft genome sequence was 3.76 Mb in length with a DNA G+C content of 69.8 mol%. Major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and 11-methyl C18 : 1ω7c, with C14 : 0 2-OH as the main hydroxy fatty acid. Ubiquinone 10 (Q-10) was the predominant respiratory quinone, and sym-homospermidine was displayed as the major polyamine. The polar lipids were composed of sphingoglycolipid, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified phospholipid and an unidentified glycolipid. The phenotypic, phylogenetic and chemotaxonomic results supported the hypothesis that strain 1PNM-20T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas lenta sp. nov. is proposed. The type strain is 1PNM-20T (=GDMCC 1.660T=DSM 27572T).

Lysobacter silvisoli sp. nov., isolated from forest soil.

A yellow-pigmented, Gram-stain-negative, gliding and rod-shaped bacterial strain, designated zong2l5T, was isolated from a forest soil sample at Dinghu Mountain, Guangdong Province, PR China. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain zong2l5T belongs to the genus Lysobacter, and was most closely related to Lysobacter enzymogenes KCTC 12131T (97.7 %) and Lysobacter soli KCTC 22011T (97.6 %). The novel strain showed an average nucleotide identity (ANI) value of 81.5 % and a digital DNA-DNA hybridization (dDDH) value of 25.3 % with L. enzymogenes KCTC 12131T based on draft genome sequences, followed by L. soli KCTC 22011T with ANI and dDDH values of 79.4 % and 22.7 %, respectively. The DNA G+C content of strain zong2l5T based on the whole genome sequence was 69.2 mol%. The major fatty acids were iso-C15 : 0, iso-C17 : 0 and summed feature 9 (iso-C17 : 1ω9c and/or 10-methyl C16 : 0). Strain zong2l5T contained Q-8 as the major isoprenoid quinone and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidyl-N-methylethanolamine, phosphatidylethanolamine, three unidentified phospholipids and an unidentified aminolipid. The phenotypic, genotypic and chemotaxonomic anlyses clearly showed that strain zong2l5T represents a novel species of the genus Lysobacter, for which the name Lysobactersilvisoli sp. nov. is proposed. The type strain is zong2l5T (=GDMCC 1.1489T=KCTC 52923T).

Satisfactory virological response and fibrosis improvement of sofosbuvir-based regimens for Chinese patients with hepatitis C virus genotype 3 infection: results of a real-world cohort study.

BACKGROUND: Chronic hepatitis C virus (HCV) genotype (GT) 3 infection with advanced liver disease has emerged as a challenging to treat by direct-acting antivirals (DAAs), but the efficacy of DAAs in Chinese HCV-GT3 patients is rarely reported. This study aimed to analyze the efficacy of sofosbuvir (SOF)-based regimens in Chinese patients with HCV-GT3 and compensated liver disease. METHODS: This was a registered retrospective study. All patients had completed at least 12 weeks SOF-based regimens therapy (with or without RBV), and were followed up for at least 24 weeks after therapy discontinuation. The primary endpoint was sustained virological response 24 weeks after end of therapy (SVR24). RESULTS: A total of 102 patients who completed at least 12 weeks therapy were finally included, with 57 in SOF + Daclatasvir (SOF + DCV), 24 in SOF + DCV + ribavirin (RBV) and 21 in SOF/Velpatasvir (SOF/VEL). The total SVR24 rate was achieved in 90.20% (92/102), with 85.96% (49/57) in SOF + DCV, 91.67% (22/24) in SOF + DCV + RBV and 100.00% (21/21) in SOF/VEL. Among 10 relapsed patients (8 in SOF + DCV and 2 in SOF + DCV + RBV), the short course (12 weeks) of therapy and no RBV addition may be the leading cause. In this cohort, the SVR24 rate was not statistically different between patients with and without cirrhosis (81.82% [27/33] vs. 94.20% [65/69], P = 0.073). Additionally, both FIB-4 (4.03 vs. 2.08, P < 0.001) and APRI (2.15 vs. 0.68, P < 0.001) scores were significant improved from baseline to week 24 after completion of therapy, regardless of the presence of cirrhosis. CONCLUSION: SOF-based regimens are highly effective in viral clearance and fibrosis remission for Chinese patients with HCV-GT3 infection. If available, SOF/VEL should be first considered.

Differential effects of ß-glucan on oxidative stress, inflammation and copper transport in two intestinal regions of large yellow croaker Larimichthys crocea under acute copper stress.

The aim of the present study was to evaluate investigate the effects of ß-glucan on oxidative stress, inflammation and copper transport in two intestinal regions of large yellow croaker under acute copper stress. Fish were injected with ß-glucan at a dose of 0 or 5 mg kg-1 body weight on 6, 4 and 2 days before exposed to 0 and 368 µg Cu L-1 for 48 h. Biochemical indicators (MDA, Cu content, MTs protein levels, Cu/Zn-SOD, CAT and iNOS activities), gene expressions of oxidative stresses (Cu/Zn-SOD, CAT, Nrf2, MTs and MTF-1), inflammatory responses (NF-κB, iNOS, IL-1ß, IL-6 and TNF-α) and Cu transporters (ATP7A, ATP7B and CTR1) were determined. In the anterior intestine, ß-glucan increased MTs levels, activities of Cu/Zn-SOD, CAT and iNOS, mRNA levels of MTs, CAT, iNOS, ATP7A and ATP7B, and reduced Cu content and CTR1 gene expression to inhibite Cu-induced MDA. But ß-glucan had no effect on inflammatory gene expressions. In the mid intestine, ß-glucan increased activities of Cu/Zn-SOD and iNOS, mRNA levels of Cu/Zn-SOD, CAT and iNOS to maintain MDA content. However, unlike the anterior intestine, ß-glucan had no effect on Cu transporter gene expressions. Furthermore, transcription factors (Nrf2, NF-κB and MTF-1) paralleled with their target genes in the mid intestine, but no correlation was observed between NF-κB and IL-1ß and TNF-α gene expressions in the anterior intestine. In conclusion, our results unambiguously showed that ß-glucan induced oxidative stress, inflammation and copper transport were varied between the anterior and mid intestines of fish under Cu stress.

Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease.

BACKGROUND Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer's disease (AD). MATERIAL AND METHODS We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The AD-specific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs. RESULTS We conducted MMIA of AD based on 1 miRNA dataset and 3 mRNA datasets derived from the Gene Expression Omnibus (GEO) database; 1759 DEGs and 12 DEmiRNAs were obtained. DEGs of AD were significantly enriched in Huntington's disease and AD. LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 were 5 DEGs regulated by 4 DEmiRNAs, including miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. These 4 miRNAs were the top 4 miRNAs covering most DEGs. According to the qRT-PCR results, the expression of PLCß2, NDUFA4, DLG4, miR-107, and miR-103a-3p was consistent with our integrated analysis. CONCLUSIONS We concluded that LRP1, CDK5R1, PLCß2, NDUFA4, and DLG4 may play a role in AD regulated by miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. Our findings will contribute to identification of biomarkers and new strategies for drug design for AD treatment.

Abrupt salinity stress induces oxidative stress via the Nrf2-Keap1 signaling pathway in large yellow croaker Pseudosciaena crocea.

The aim of the present study was to evaluate the effects of abrupt salinity stress (12, 26 (control), and 40) on lipid peroxidation, activities and mRNA levels of antioxidant enzymes (Cu/Zn-SOD, CAT, GPx, and GR), and gene expression of the Nrf2-Keap1 signaling molecules at different times (6, 12, 24, and 48 h) in the liver of large yellow croaker Pseudosciaena crocea. The results showed that lipid peroxidation was sharply reduced at 6 h and increased at 12 h before returning to control levels in the hypo-salinity group. Similarly, lipid peroxidation was significantly decreased at 6 h followed by a sharp increase towards the end of the exposure in the hyper-salinity group. Negative relationships between lipid peroxidation and antioxidant enzyme activities and positive relationships between activities and gene expression of antioxidant enzymes were observed, suggesting that the changes at molecular levels and enzyme activity levels may provide protective roles against damage from salinity stress. Obtained results also showed a coordinated transcriptional regulation of antioxidant genes, suggesting that Nrf2 is required for regulating these genes. Furthermore, there was a positive relationship between the mRNA levels of Nrf2 and Keap1, indicating that Keap1 plays an important role in switching off the Nrf2 response. In conclusion, this is the first study to elucidate effects of salinity stress on antioxidant responses in large yellow croaker through the Keap1-Nrf2 pathway.