Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a response-guided therapy strategy.

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Selectfluor Mediated Direct C-H Fluorination of 3-Heteroaryl-Oxindoles.

An efficient transition-metal-free fluorination synthesis of N-H-free 3-heteroaryl-oxindoles with Selectfluor was depicted. Under mild reaction conditions, a series of 3-heteroaryl-fluorooxindoles were produced in yield of 62-88% using Selectfluor as a fluorine source.

Signal Transduction Associated with Mn-induced Neurological Dysfunction.

Manganese (Mn) is a heavy metal that occurs widely in nature and has a vital physiological role in growth and development. However, excessive exposure to Mn can cause neurological damage, especially cognitive dysfunction, such as learning disability and memory loss. Numerous studies on the mechanisms of Mn-induced nervous system damage found that this metal targets a variety of metabolic pathways, for example, endoplasmic reticulum stress, apoptosis, neuroinflammation, cellular signaling pathway changes, and neurotransmitter metabolism interference. This article reviews the latest research progress on multiple signaling pathways related to Mn-induced neurological dysfunction.

Effects of sodium para-aminosalicylic acid on chelation treatment in Pb-exposed mice.

Lead (Pb) is a corrosion-resistant, heavy, non-ferrous metal. Several metal chelators have been used for the treatment of Pb poisoning. However, the efficacy of sodium para-aminosalicylic acid (PAS-Na) in enhancing Pb excretion has yet to be fully characterized. Healthy male mice (90) were divided into six groups, the normal control group was intraperitoneally (i.p.) injected with saline and the remaining group of mice i.p. 120 mg/kg Pb acetate. Four hour later, mice were subcutaneously (back) injected (s.c.) with (80, 160, 240 mg/kg) PAS-Na or 240 mg/kg edetate calcium disodium (CaNa2EDTA) or an equivalent amount of saline, once per day for 6 days. After 24-h urine sample collections, the animals were anesthetized with 5% chloral hydrate and sacrificed in batches on the 2nd, 4th, or 6th day. Levels of Pb [including manganese (Mn) and copper (Cu)] in the urine, whole blood, and brain tissues were analyzed by graphite furnace atomic absorption spectrometry. The results showed that Pb exposure increased its levels in urine and blood, and PAS-Na treatment may afford antagonistic effect on Pb poisoning, suggesting that PAS-Na is a potentially effective treatment to promote excretion of Pb.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

BACKGROUND: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife. METHODS: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years. Distinct trajectories of systolic blood pressure (SBP), body mass index (BMI), and heart rate from childhood to midlife were identified by group-based trajectory modeling. Vascular aging was assessed by carotid intima media thickness or brachial-ankle pulse wave velocity. RESULTS: We identified 4 distinct SBP trajectories, 3 distinct BMI trajectories, and 2 distinct heart rate trajectories from childhood to midlife. Persistently increasing SBP, high-increasing BMI, and high-stable heart rate were all shown to have a positive association with brachial-ankle pulse wave velocity in midlife. For carotid intima-media thickness, similar associations were observed for persistently increasing SBP and high-increasing body mass index. After further adjustment for SBP, body mass index and heart rate at the time of vascular assessment in 2017, associations were also observed for cardiovascular risk factor trajectories accumulation with brachial-ankle pulse wave velocity (ß, 0.656 [95% CI, 0.265-1.047]) and with carotid intima media thickness (ß, 0.045 [95% CI, 0.011-0.079]) in adulthood. CONCLUSIONS: Longitudinal exposure to individual cardiovascular risk factors from childhood to midlife and cardiovascular risk factor accumulation were associated with an increased risk of vascular aging in midlife. Our study lends support for early targeting of risk factors in order to prevent cardiovascular disease later in life.

Protective Effects of Sodium Para-Aminosalicylic Acid on Lead and Cadmium Co-Exposure in SH-SY5Y Cells.

BACKGROUND: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. METHODS: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. RESULTS: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 µmol/L lead, 0.25 µmol/L cadmium, and 1-fold Pb-Cd mixture (1 µmol/L Pb + 0.25 µmol/L Cd), while 10-fold Pb-Cd combined exposure (10 µmol/L Pb + 2.5 µmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 µmol/L Pb + 2.5 µmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. CONCLUSION: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.

Sodium para-aminosalicylic acid ameliorates brain neuroinflammation and behavioral deficits in juvenile lead-exposed rats by modulating MAPK signaling pathway and alpha-synuclein.

Lead (Pb) is a developmental neurotoxin that can disrupt brain development and damage the brain regions responsible for executive function, behavioral regulation and fine motor control. Sodium para-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that can cross the blood-brain barrier. The purpose of this study was to examine the effects of juvenile rat Pb exposure on behavioral changes and brain inflammation, and the efficacy of PAS-Na in ameliorating these effects. The results showed that Pb exposure during the juvenile period (from weaning to adult period) delayed rats' growth development and impaired their motor learning. Pb exposure not only increased Pb concentrations in several brain regions (including hippocampus, striatum and substantia nigra), but also disrupted metal-homeostasis in the brain, as higher levels of iron (Fe) and calcium (Ca) were observed in the substantia nigra. Moreover, Pb activated the MAPK pathway and increased levels of inflammatory factors such as IL-1ß, TNF-α and IL-6 in the hippocampus, striatum and substantia nigra. Furthermore, Pb increased the levels of alpha-synuclein (α-syn) in these brain sites. PAS-Na improved the motor deficits and brain inflammation in the Pb-exposed rats. Moreover, the elevated Pb, Fe and Ca concentrations in the brain were significantly reduced by PAS-Na, which contains amino, carboxyl and hydroxyl functional groups, suggesting that it may act as a chelator of brain metals. In addition, PAS-Na inhibited the Pb-induced MAPK pathway activation and α-syn accumulation in the same brain regions. Taken together, our novel study suggest that PAS-Na shows efficacy in improving the Pb-induced behavioral changes in rats by inhibiting MAPK-dependent inflammatory pathways and reducing α-syn accumulation.

Methylcyclopentadienyl Manganese Tricarbonyl Alter Behavior and Cause Ultrastructural Changes in the Substantia Nigra of Rats: Comparison with Inorganic Manganese Chloride.

The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl2) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl2. After adaptive feeding for 7 days, male and female Sprague-Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl2·4H2O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT's propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl2-treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl2 groups. In summary, these findings suggest that MMT and MnCl2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl2's manifestations of atypical parkinsonism.

Cost-effectiveness analysis of 4 GLP-1RAs in the treatment of obesity in a US setting.

Background: The number of obese people continues to increase worldwide, and obesity-related complications add to every country's health burden. Consequently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are attracting increasing attention. This study sought to assess the cost effectiveness for weight loss of 4 GLP-1RAs in adult patients with obesity in the United States. Methods: Four GLP-1RA groups that received Liraglutide (1.8 mg QD), Semaglutide (1.0 mg QW), Dulaglutide (1.5 mg QW), or Exenatide (10 µg BID), and one no-treatment group were compared using a decision-tree model. All the estimated parameters were derived from published articles. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were adopted as the study endpoints. We analyzed the results with the willingness-to-pay (WTP) threshold, and conducted deterministic and probabilistic sensitivity analyses. Results: The GLP-1RAs produced effective weight-loss results; however, not all the GLP-1RAs were cost effective compared to no treatment based on a WTP threshold of $195000/QALY. Among the 4 GLP-1RAs, Semaglutide provided a cost-effective strategy with an ICER of $135467/QALY. The sensitivity analyses showed that these results are reliable. Conclusions: Among the 4 GLP-1RAs, Semaglutide was the most cost-effective obesity medication.

Successful upgrade to cardiac resynchronization therapy for cardiac implantation-associated left subclavian vein occlusion: A case report.

BACKGROUND: Subclavian vein stenosis or occlusion may be caused by a transvenous pacemaker, which makes the reimplantation of a new pacemaker lead difficult. Transvenous pacemaker lead implantation-related subclavian vein occlusion may present difficulty with regard to cardiac resynchronization therapy (CRT) upgrade. CASE SUMMARY: We report the case of a 46-year-old man who was admitted with total subclavian vein occlusion caused by a permanent pacemaker that had been implanted 2 years previously. We successfully treated this patient with an upgrade to a CRT pacemaker by utilizing transferable interventional coronary and radiological techniques. The patient recovered uneventfully during the follow-up period. CONCLUSION: CRT upgrade is still a viable technique for the treatment of subclavian vein obstruction caused by previous pacemaker implantation.

Comparison of Proteomics Profiles Between Xenografts Derived from Cell Lines and Primary Tumors of Thyroid Carcinoma.

Patient-consistent xenograft model is a challenge for all cancers but particularly for thyroid cancer, which shows some of the greatest genetic divergence between human tumors and cell lines. In this study, proteomic profiles of tumor tissues from patients, included anaplastic thyroid carcinoma (ATC) and papillary thyroid carcinoma, and xenografts (8305C, 8505C, FRO, BAPAP and IHH4) were obtained using HPLC-tandem mass spectrometry and compared based on all proteins detected (3,961), cancer-related proteins and druggable proteins using pairwise Pearson's correlation analysis. The human tissue showed low proteomic similarity to the ATC cell lines (8305C, r = 0.344-0.416; 8505C, 0.47-0.579; FRO, 0.267-0.307) and to PTC cell lines (BCPAP, 0.303-0.468; IHH4, 0.262-0.509). Human tissue showed the following similarity to cell lines at the level of 135 cancer-related pathways. The ATC cell lines contained 47.4% of the cancer-related pathways (19.26%-33.33%), while the PTC cell lines contained 40% (BCPAP, 25.93%; IHH4, 28.89%). In patient tumor tissues, 44-60 of 76 and 52-53 of 93 druggable proteins were identified in ATC and PTC tumors, respectively. Ten and 29 druggable proteins were not identified in any of the ATC and PTC xenografts, respectively. We provide a reference for CDX selecting in in vivo studies of thyroid cancer.

Destrin Contributes to Lung Adenocarcinoma Progression by Activating Wnt/ß-Catenin Signaling Pathway.

Lung cancer, especially lung adenocarcinoma, is one of the most common neoplasms worldwide. However, the mechanisms underlying its initiation, development, and metastasis are still poorly understood. Destrin (DSTN) is a member of ADF/cofilin family. Its detailed biological function remains unknown, although it is reported that DSTN is involved in cytoskeleton remodeling and regulation of actin filament turnover. Recent evidence has shown that high expression of cofilin-1 is associated with invasion and poor prognosis of several types of human tumors, but the detailed mechanism is still entirely unclear, particularly in lung cancer tumorigenesis and malignancy. Here, we report that DSTN was highly expressed in a mouse lung cancer model induced by urethane and in clinical lung adenocarcinoma tissue samples. Its expression level was positively correlated with cancer development, as well as metastasis to the liver and lymph nodes. Consistently, it was directly associated with the poor prognosis of lung adenocarcinoma patients. Furthermore, we also found that DSTN promotes cell proliferation, invasion, and migration in vitro, and facilitates subcutaneous tumor formation and lung metastasis via intravenous injection in vivo. Mechanically, DSTN associates with and facilitates nuclear translocation of ß-catenin, which promotes epithelial-to-mesenchymal transition (EMT). Taken together, our results indicated that DSTN enhances lung cancer malignancy through facilitating ß-catenin nuclear translocation and inducing EMT. Combined with multivariate analyses, DSTN might potentially serve as a therapeutic target and an independent prognostic marker of lung adenocarcinoma. IMPLICATIONS: This finding indicates that DSTN facilitates ß-catenin nuclear translocation and promotes malignancy in lung adenocarcinoma.

Gimesia benthica sp. nov., a planctomycete isolated from a deep-sea water sample of the Northwest Indian Ocean.

A Gram-stain-negative, stalked, oval-shaped and budding bacterial strain, designated E7T, was isolated from a deep-sea water sample collected from the Northwest Indian Ocean. The novel strain was strictly aerobic, and catalase- and oxidase-positive. It grew at 6-40 °C (optimum 30 °C) and pH 5.5-8.0 (optimum pH 7.0-7.5). The strain required 0.5-9.0 % (w/v) NaCl (optimum 3.0-5.0 %) for growth. Aesculin, starch, pectin and Tween 20 were hydrolysed. Based on 16S rRNA gene sequence analysis, strain E7T showed the highest similarity with Gimesia maris DSM 8797T (97.5 %). The average nucleotide identity and in silico DNA-DNA hybridization values between strain E7T and G. maris DSM 8797T were 78.0 and 19.3 %, respectively. The predominant cellular fatty acids of strain E7T were C16 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The major respiratory quinone was menaquinone-6 (MK-6) and the major polar lipids were phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PMME), phosphatidyldimethylethanolamine (PDME), phosphatidylcholine (PC) and diphosphatidylglycerol (DPG). The genomic DNA G+C content of strain E7T was 52.8 mol%. On the basis of phylogenetic inference and phenotypic characteristics, it is proposed that strain E7T represents a novel species of the genus Gimesia, for which the name Gimesia benthica sp. nov. is proposed. The type strain is E7T (=CGMCC 1.16119T=KCTC 72737T).

Halovulum marinum sp. nov., isolated from deep-sea water of the Indian Ocean, and emended description of the genus Halovulum.

A novel Gram-stain-negative, aerobic, motile by peritrichous flagella, oval to rod-shaped bacterium, designated strain 2CG4T, was isolated from a deep-sea water sample collected from the Northwest Indian Ocean. The results of phylogenetic analysis of both 16S rRNA gene and RpoC protein sequences indicated that this strain was affiliated with the genus Halovulum in the Amaricoccus clade of the family Rhodobacteraceae of the class Alphaproteobacteria, sharing 95.3 % similarity at the 16S rRNA gene sequence level with the type strain of Halovulum dunhuangense YYQ-30T, the only species in the genus Halovulum. The predominant fatty acids (>10 %) of 2CG4T were summed feature 8 (C18 : 1ω7c and/ or C18 : 1ω6c; 61.1 %) and cyclo-C19 : 0ω8c (15.6 %). The polar lipids of 2CG4T were phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and sulfoquinovosyldiacylglycerol. The only isoprenoid quinone of 2CG4T was ubiquinone-10. The DNA G+C content of 2CG4T was determined to be 69.4 %. The central gene pufLM for the photosynthetic reaction was not detected. No growth occurred for 2CG4T in the absence of NaCl. On the basis of these data, it is concluded that the 2CG4T represents a novel species of the genus Halovulum, for which the name Halovulum marinum sp. nov. is proposed. The type strain is 2CG4T (=CGMCC 1.16468T=JCM 32611T).

Preventive Effect and Mechanism of Ethyl Acetate Extract of Sceptridium ternatum in Monocrotaline-Induced Pulmonary Arterial Hypertension.

OBJECTIVE: To observe the effect and molecular mechanism of ethyl acetate extract of Sceptridium ternatum (STE) on the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). METHODS: The main chemical components of Sceptridium ternatum were determined, and the effects in PAH rats were observed. A total of 140 Sprague Dawley rats were randomly and equally divided into the normal group, the model group, the Bosentan group, and the STE groups (2.5, 5, 10 g/kg) by the random number table method. The characteristic indicators of PAH were measured, and immunohistochemistry was used to observe the lung tissue of rats. Morphological changes of the lung tissue were observed under the light microscope. RESULTS: Compared with the normal group, rats in the model group showed a significant increase in right ventricular free wall thickness (RVFWT), mean pulmonary arterial pressure (mPAP), mean right ventricular pressure (mRVP), max right ventricular pressure (max RVP), weight of right ventricle (RV), and lung index (LI), while a significant decrease in pulmonary artery acceleration time (PAAT, P<0.01). Compared with the model group, rats treated with STE had a significant decrease of RVFWT, mPAP, mRVP, max RVP, and RV, while a significant increase of PAAT (P<0.01). After injection of MCT, nuclear factor- κB (NF- κB) p65 and α -smooth muscle actin (α -SMA) expression levels were up-regulated, and on the contrary, the treatment groups showed a significant down-regulation without dose-dependent trend. CONCLUSIONS: STE can relieve the PAH in rats. STE may relieve pulmonary vascular disease and pulmonary injury by down-regulating the expression of NF- κB p65 and α -SMA.

Elevated proportion of collapsed microvessels indicate poor survival outcome in patients with non-small cell lung cancer.

BACKGROUND: An integral and well-functioning vascular system is essential for tumor progression and chemotherapy infusion. However, the lumen integrity of the microvessels and its significance in prognosis has not been studied. In this study, we found that the proportion of collapsed microvessels is suggested to be a novel biomarker for predicting prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, immunohistochemical CD31 staining was performed to identify the microvessels in tumor specimens. Proportions of collapsed vessels were estimated in CD31-stained tumor specimens from 100 patients with NSCLC. The correlation between collapsed microvessel proportion and survival time were evaluated by univariate and multivariate analysis. RESULTS: Data from 99 patients were analyzed and a wide range of collapse-microvessel fraction was observed in 96 patients (1.4%-70%). Elevated collapse proportion (⩾6.5%) indicated poor overall survival in both univariate analysis (p = 0.042) and multivariate analysis (p = 0.014). CONCLUSIONS: Elevated proportion of collapsed microvessels indicted poor survival outcome in patients with NSCLC.

Hyphobacterium indicum sp. nov., isolated from deep seawater, and emended description of the genus Hyphobacterium.

A novel aerobic, Gram-stain-negative bacterium, designated strain 2ED5T, was isolated from a deep seawater sample in the north-west Indian Ocean. Cells of the strain were oval- to rod-shaped, and motile by a polar flagellum or sessile by a prostheca. The strain formed creamy white colonies on 2216E marine agar plates. It grew at 10-40 °C (optimum 28 °C) and pH 5.0-8.0 (optimum pH 6.0-7.0). The strain required 1-6 % (w/v) NaCl for growth and grew optimally in the presence of 2-3 % NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain 2ED5T was affiliated with the genus Hyphobacterium in the family Hyphomonadaceae of the class Alphaproteobacteria, sharing 95.1 % similarity at the 16S rRNA gene sequence level with the type strain of Hyphobacterium vulgare, the only species in the genus Hyphobacterium. The major fatty acids of the strain were C18 : 1ω7c and iso-C17 : 1ω9c, and the polar lipids included monoglycosyl diglyceride, sulfoquinovosyl diacylglycerol, glucuronopyranosyl diglyceride, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and an unidentified glycolipid. The strain contained ubiquinone Q-10 as the predominant respiratory quinone. The G+C content of the genomic DNA of the strain was 60.9 mol%. Based on the results of this polyphasic analysis, strain 2ED5T represents a novel species in the genus Hyphobacterium, for which the name Hyphobacterium indicum sp. nov. is proposed. The type strain is 2ED5T (=CGMCC 1.16466T=JCM 32612T).

Characterization of bacteria and yeasts isolated from traditional fermentation starter (Fen-Daqu) through a 1H NMR-based metabolomics approach.

Daqu is a traditional fermentation starter for the production of baijiu and vinegar. It is an important saccharifying and fermenting agent associated with alcoholic fermentation and also a determining factor for the flavour development of these products. Bacterial and yeast isolates from a traditional fermentation starter (Fen-Daqu) were examined for their amylolytic activity, ethanol tolerance and metabolite production during sorghum-based laboratory-scale alcoholic fermentation. The selected strains (Bacillus licheniformis, Pediococcus pentosaceus, Lactobacillus plantarum, Pichia kudriavzevii, Wickerhamomyces anomalus, Saccharomyces cerevisiae, and Saccharomycopsis fibuligera) were blended in different combinations, omitting one particular strain in each mixture. 1H nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis was used to investigate the influence of the selected strains on the metabolic changes observed under the different laboratory-controlled fermentation conditions. Principal component analysis showed differences in the metabolites produced by different mixtures of pure cultures. S. cerevisiae was found to be superior to other species with respect to ethanol production. S. fibuligera and B. licheniformis converted starch or polysaccharides to soluble sugars. Lactic acid bacteria had high amylolytic and proteolytic activities, thereby contributing to increased saccharification and protein degradation. W. anomalus was found to have a positive effect on the flavour of the Daqu-derived product. This study highlights the specific functions of S. cerevisiae, S. fibuligera, B. licheniformis, W. anomalus and lactic acid bacteria in the production of light-flavour baijiu (fen-jiu). Our results show that all investigated species deliver an important contribution to the functionality of the fermentation starter Daqu.

Validation of the China-PAR Equations for Cardio-cerebrovascular Risk Prediction in the Inner Mongolian Population.

The objective of this study was to evaluate the usefulness of the China-PAR equations in predicting the 10-year risk of cardiovascular disease (CVD) in the Inner Mongolians population. A population-based, prospective cohort of 2,589 Mongolians were followed up from 2003 to 2012. Participants were categorized into 4 subgroups according to their 10-year CVD risks calculated using the China-PAR equations: < 5%, 5%-9.9%, 10%-19.9%, and ⪖ 20%. The China-PAR equations discriminated well with good C statistics (range, 0.76-0.86). The adjusted hazard ratios for CVD showed an increasing trend among the 4 subgroups (P for trend < 0.01). However, the China-PAR equations underestimated the 10-year CVD risk in Mongolians, and the calibration was unsatisfactory (Hosmer-Lemeshow χ2 = 19.98, P < 0.01 for men, χ2 = 46.58, P < 0.001 for women). The performance of the China-PAR equations warrants further validation in other ethnic groups in China.