Comparison of cryobiopsy and forceps biopsy for the diagnosis of mediastinal lesions: A randomised clinical trial.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard approach for lung cancer staging. However, its diagnostic utility for other mediastinal diseases might be hampered by the limited tissue retrieved. Recent evidence suggests the novel sampling strategies of forceps biopsy and cryobiopsy as auxiliary techniques to EBUS-TBNA, considering their capacity for larger diagnostic samples. METHODS: This study determined the added value of forceps biopsy and cryobiopsy for the diagnosis of mediastinal diseases. Consecutive patients with mediastinal lesions of 1 cm or more in the short axis were enrolled. Following completion of needle aspiration, three forceps biopsies and one cryobiopsy were performed in a randomised pattern. Primary endpoints included diagnostic yield defined as the percentage of patients for whom mediastinal biopsy led to a definite diagnosis, and procedure-related complications. RESULTS: In total, 155 patients were recruited and randomly assigned. Supplementing EBUS-TBNA with either forceps biopsy or cryobiopsy increased diagnostic yield, with no significant difference between EBUS-TBNA plus forceps biopsy and EBUS-TBNA plus cryobiopsy (85.7 % versus 91.6 %, P = 0.106). Yet, samples obtained by additional cryobiopsies were more qualified for lung cancer molecular testing than those from forceps biopsies (100.0 % versus 89.5 %, P = 0.036). When compared directly, the overall diagnostic yield of cryobiopsy was superior to forceps biopsy (85.7 % versus 70.8 %, P = 0.001). Cryobiopsies produced greater samples in shorter procedural time than forceps biopsies. Two (1.3 %) cases of postprocedural pneumothorax were detected. CONCLUSIONS: Transbronchial mediastinal cryobiopsy might be a promising complementary tool to supplement traditional needle biopsy for increased diagnostic yield and tissue harvesting. TRIAL REGISTRATION: ChiCTR2000030373.

[Quality of life and risk factors in patients with herpes zoster].

Objective: To evaluate the quality of life and influencing factors of patients with herpes zoster (HZ) seen in hospitals. Methods: Based on Zoster Brief Pain Inventory (ZBPI) and Five-level EuroQol Five-dimensional Questionnaire (EQ-5D-5L), a cross-sectional survey was conducted to evaluate the pain severity and quality of life of 332 HZ cases seen in 22 hospitals of Lu'an City (Anhui Province), Zibo City (Shandong Province) and Tongchuan City (Shaanxi Province) from October to December 2021. The censored least absolute deviations (CLAD) model was used to analyze the related factors affecting the changes of patients' health utility values. Results: The 45.5% of 332 HZ cases were male. The median (Q1,Q3) age was 59 (50, 68) years. 59.64% of them assessed by ZBPI had moderate to severe pain in the past 24 hours (worst pain score≥5), and that of PHN cases was 84.8%(39/46). 77.7% (258/332), 77.4% (257/332) and 74.1% (246/332) of all patients reported that pain interfered with sleep, mood and general activities, respectively. Aging [ß40-49y (95%CI)=-0.11 (-0.15, -0.08); ß50-59y (95%CI)=-0.03 (-0.05, 0.00); ß60-69y (95%CI)=-0.09 (-0.12, -0.06); ß70-90y(95%CI)=-0.16 (-0.19, -0.12)], working status (unemployed) [ßfarmer (95%CI)=0.15 (0.13, 0.18); ßretirees(95%CI)=0.21 (0.18, 0.24); ßemployee (95%CI)=0.13 (0.10, 0.16) ], complications[ßPHN (95%CI)=-0.08 (-0.13, -0.04); ßother complications (95%CI)=-0.12 (-0.15, -0.08)], within 30 days after onset [ß(95%CI)=-0.01 (-0.03, 0.01)] and treatment [ßother complications (95%CI)=-0.09 (-0.11, -0.06)] were related factors for the decline of health utility value (all P values <0.05). Conclusions: More than half of the patients with HZ had moderate to severe pain in the past 24 hours, which had a serious negative impact on the physical and mental health of the patients. Elderly patients, acute patients and patients with complications had lower health utility values and worse health status. We suggest that eligible people be vaccinated with HZ vaccine as soon as possible.

Association of major adverse cardiovascular events and cardiac troponin-I levels following percutaneous coronary intervention: a three-year follow-up study at a single center.

OBJECTIVE: Major adverse cardiovascular events occurrences of patients with different cardiac troponin-I (cTnI) levels following percutaneous coronary intervention (PCI) remained controversial. The prognostic relevance and risk factors of PCI-related myocardial infarction (MI) were not very clear as well. PATIENTS AND METHODS: Our study included 249 coronary artery disease patients without preoperative cTnI elevation who successfully accepted PCI from 2013 to 2014. A three-year follow-up was conducted for each patient. The patients were divided into PCI-related MI group and non-PCI-related MI group. Risk factors of PCI-related MI were first explored. The occurrence of MACE was recorded. The prognostic relevance between PCI-related MI (PMI) group and non-PCI-related MI group, as well as different postoperative cTnI levels, were compared. RESULTS: Low-density lipoprotein cholesterol (LDL-C), age, Gensini Score, total stent length, and intra-operative complication were found positively correlated with PCI-related MI occurrence, while hemoglobin and prior PCI history were negatively correlated. After 3-year follow-up, the Kaplan-Meier survival curve showed MACE occurrence was significantly increased in PCI-related MI group. Comparing to patients with normal postoperative cTnI, MACE occurrence was increased in patients with a 10×upper limit of normal (ULN)≤cTnI<70×ULN and cTnI≥70×ULN, while there was no difference in patients with 1×ULN≤cTnI<5×ULN and 5×ULN≤cTnI<10×ULN. Cox proportional hazard regression analysis revealed PMI, NT-proBNP, and left ventricular ejection function (LVEF)<50% were positively correlated with MACE occurrence, while maximum inflation pressure and apoA-I were negatively correlated. CONCLUSIONS: Prognosis of PCI-related MI was poor, as well as in patients with postoperative cTnI≥10×ULN. Among the risk factors of PMI, LDL-C, age, Gensini Score, total stent length, and intra-operative complication were positively correlated with PCI-related MI occurrence, while hemoglobin and prior PCI history were negatively correlated.

Bioconversion of Hg0 into HA-Hg for simultaneous removal of Hg0 and NO in a denitrifying membrane biofilm reactor.

Bacterial mercury oxidation coupled to denitrification offers great potential for simultaneous removal of elemental mercury (Hg0) and nitric oxide (NO) in a denitrifying membrane biofilm reactor (MBfR). Four potentially contributory mechanisms tested separately, namely, membrane gas separation, medium absorption, biosorption and biotransformation, which contributed 4.9%/7.2%, 8.1%/8.9%, 38.8%/9.5% and 48.2%/84.9% of overall Hg0/NO removal in MBfR. Herein, Hg0 bio-oxidation, oxidative Hg0 biosorption and denitrification played leading roles in simultaneous removal of Hg0 and NO. Living microbes performed simultaneous Hg0 bio-oxidation and denitrification, in which Hg0 as electron donor was biologically oxidized to oxidized mercury (Hg2+), while NO as the terminal electron acceptor was denitrified to N2. The Hg2+ further complexed with humic acids in extracellular polymeric substances via functional groups (-SH, -OH, -NH- and -COO-) and formed humic acids bound mercury (HA-Hg). Non-living microbial matrix performed oxidative Hg0 biosorption, in which Hg0 may be physically adsorbed by cellular matrix, then non-metabolically oxidized to Hg2+ via oxidative complexation with -SH in humic acids and finally cleavage of S-H bond and surface charge transfer led to formation of HA-Hg. Therefore, bioconversion of Hg0 to HA-Hg by Hg0 bio-oxidation and oxidative Hg0 biosorption coupled with NO denitrification to N2 dynamically cooperated to accomplish simultaneous removal of Hg0 and NO in MBfR.

Photocatalytic membrane combined with biodegradation for toluene oxidation.

Photocatalytic membrane coupled to biodegradation offers potential for degrading volatile organic compounds (VOCs) in photocatalytic membrane biofilm reactor. An intimately coupled photocatalysis and biodegradation reactor was operated in continuous operation for 500 days to treat simulated waste gas containing toluene. Toluene removal efficiency obtained 99%, with the elimination capacity of 550 g m-3·h-1. Membrane photocatalysis coupled to biodegradation was created to improve toluene removal from 11 to 20%. The dominant genera were Lysinibacillus, Hydrogenophaga, Pseudomonas at 30 d, Rudaea, Dongia, Litorilinea at 230 d xyl, Tod, Tcb, Bed, Tmo, Tbu, Tou, Dmp, Cat were functional genes of toluene metabolism, as shown by16S rDNA and metagenomic sequencing. Photocatalysis destroyed part of the toluene into biodegradable intermediates that were immediately mineralized by microorganisms in biofilm, some toluene was directly degraded by toluene degrading bacterial community into carbon dioxide and water. The novel hybrid photocatalytic membrane biofilm reactor is a cost-effective and robust alternative to VOCs treatment.

Simultaneous mercury oxidation and NO reduction in a membrane biofilm reactor.

This work demonstrates bacterial oxidation of mercury (Hg0) coupled to nitric oxide (NO) reduction in a denitrifying membrane biofilm reactor (MBfR). In 93 days' operation, Hg0 and NO removal efficiency attained 90.7% and 74.1%, respectively. Thauera, Pseudomonas, Paracoccus and Pannonibacter played dual roles as Hg0 oxidizers and denitrifiers simultaneously. Denitrifying bacteria and the potential mercury resistant bacteria dominated the bacterial community. Denitrification-related genes (norB, norC, norD, norE, norQ and norV) and enzymatic Hg0 oxidation-related genes (katG, katE) were responsible for bacterial oxidation of Hg0 and NO reduction, as shown by metagenomic sequencing. XPS, HPLC-ICP-MS and SEM-EDS indicated the formation of a stable mercuric species (Hg2+) reasulting from Hg0 oxidation in the biofilm. Bacterial oxidation of Hg0 was coupled to NO reduction in which Hg0 served as the initial electron donor while NO served as the terminal electron acceptor and thereby redox between Hg0 and NO was formed. MBfR was capable of both Hg0 bio-oxidation and denitrifying NO reduction. This research opens up new possibilities for application of MBfR to simultaneous flue gas demercuration and denitration.

[Screening for precursors of colorectal cancer].

Screening has been proven to be effective for the control of colorectal cancer (CRC). The target of CRC screening is shifting from CRC to colorectal neoplasia (CN), the precursors of CRC. Based on the the latest national guideline, the Consensus of Screening for CRC and CN, and the recent research of precursors both at home and abroad. This paper summarizes the progress in the research of risk factors, risk prediction model, screening strategy optimization, colonoscopy quality control, sessile serrated adenoma identification and follow up as well as the recognition of precursors.

Higher peripheral neutrophil and monocyte counts are independent indicators of the presence and severity of proteinuria in apparently normal adults.

BACKGROUND: Proteinuria reflects disrupted renal function in which enhanced immuno-inflammation activity plays a key role. So far, information concerning the relations between proteinuria and peripheral different leucocyte counts is limited. We thereby conducted this study aiming to obtain comprehensive information of the issue. METHODS: Study subjects were participants of a health check programme from 2000 to 2002. Additional two enrolment criteria were (i) leucocyte analysis was checked with a same blood cell counter and (ii) urinalysis showed no pyuria or haematuria. Data of subjects were retrospectively collected and analysed by using sas program. RESULTS: Higher neutrophil and monocyte counts, but not lymphocyte count, were significantly associated with both the presence and the severity of proteinuria (all P < 0.0001, n= 12 225). Such associations maintained significant after adjustments of age, sex, body mass index, mean blood pressure and blood levels of glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides and creatinine (all P< or = 0.001, n= 12 225). There was a sharp increase in the incidence of proteinuria in association with a neutrophil count > or =4.50 x 10(9)/L (P< or = 0.0001). CONCLUSION: Our study showed that in apparently normal adults the presence and the severity of proteinuria could be reflected by the peripheral neutrophil and monocyte counts, but not the lymphocyte count. These findings, together with the documented inflammatory basis of proteinuria and the diverse pathophysiological roles of differential leucocytes, suggest that peripheral differential leucocyte counting may be useful in predicting the course of an existing proteinuria. Perspective longitudinal follow-up studies are needed to test this presumption.

Salvianolic acid A inhibits platelet activation and arterial thrombosis via inhibition of phosphoinositide 3-kinase.

BACKGROUND AND OBJECTIVE: Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia miltiorrhiza Bunge, a herb that is widely used for atherothrombotic disease treatment in Asian medicine. As platelets play pivotal roles in atherothrombogenesis, we studied the effect of SAA on platelet activation and its underlying mechanisms. METHODS AND RESULTS: SAA dose-dependently inhibited platelet aggregation induced by ADP, thrombin, collagen and U46619. It reduced ADP-enhanced platelet P-selectin expression and fibrinogen binding, which consequently hampered ADP-induced platelet-leukocyte aggregation. SAA also inhibited platelet spreading on fibrinogen, a process mediated by outside-in signaling. Under an arterial shear rate of 1000 s(-1), SAA decreased platelet adhesion on collagen surfaces by approximately 40%. Western blot analysis showed that SAA, like the phosphoinositide 3-kinase (PI3K) inhibitors LY294002 and TGX-221, potently inhibited PI3K, as shown by reduced Akt phosphorylation. The in vitro findings were further evaluated in the mouse model of arterial thrombosis, in which SAA prolonged the mesenteric arterial occlusion time in wild-type mice (35 + or - 2 min without SAA and 56 + or - 4 min with SAA; P < 0.01). Interestingly, SAA could even counteract the shortened arterial occlusion time in Ldlr(tm1Her) mutant mice (21 + or - 2 min without SAA and 45 + or - 4 min with SAA; P < 0.01). CONCLUSIONS: SAA inhibits platelet activation via the inhibition of PI3K, and attenuates arterial thrombus formation in vivo. Our data suggest that SAA may be developed as a novel therapeutic agent for the prevention of thrombotic disorders.

Expression of aberrant beta-catenin and impaired p63 in craniopharyngiomas.

Craniopharyngiomas are rare, histologically benign, non-neuroepithelial epithelial tumors arising from the sellar region, the molecular pathogenesis of CPs is yet not understood. The aim of the present study was to assess expression of aberrant beta-catenin and impaired p63 in 66 craniopharyngiomas included 51 adamantinomatous craniopharyngiomas and 15 squamous papillary craniopharyngiomas. On immunohistochemistry, 47 out of 51 adamantinomatous craniopharyngiomas, but not squamous papillary craniopharyngiomas, showed strong nuclear/cytoplasmic expression for beta-catenin predominantly in compactly cohesive epithelial cells within the whorl-like arrays where ki-67 was almost absent and rarely in palisaded cells where ki-67 was mainly present. P63 overexpression was observed in 45 out of 51 adamantinomatous craniopharyngiomas and 14 out of 15 squamous papillary craniopharyngiomas. P63 stained not only in the nuclei of basal layer cells but also within the whorl-like arrays in adamantinomatous craniopharyngiomas and uniformly in squamous papillary craniopharyngiomas. Using quantitative real time polymerase chain reaction techniques to correlate p63 protein expression with p63 mRNA levels, TAp63 isoforms mRNA was reduced, whereas DeltaNp63 mRNA elevated at levels in 5 snap frozen tissue samples with multiple large p63 positive cell clusters compared with normal tissues. In conclusion, the present study confirmed that the two variants of CPs have genetically not only distinctive but also common feature. It demonstrated that cytoplasm/nuclear beta-catenin accumulation is an exclusively characteristic morphology of adaCPs. P63 immunohistochemical overexpression were found in both adaCPs and spCPs variant when analyzed in the same study. Taken together, the impaired p63 expression may be attributed to elevated DeltaNp63 mRNA and reduced TAp63mRNA in CPs.

Synthesis, DNA binding and cytotoxicity of new pyrazole emodin derivatives.

A series of new anthrapyrazoles were derived from emodin by attaching various cationic alkyl amino side chains onto a pyrazole ring which had been incorporated into the anthraquinone chromophore. Compared with emodin, the derivatives had significantly higher DNA binding affinity based on interaction with calf thymus DNA, and much more potent cytotoxicity against different tumor cells. The derivatives with a mono-cationic alkyl side chain exhibited the highest DNA binding affinity and cytotoxicity.

Senescence and telomere shortening induced by novel potent G-quadruplex interactive agents, quindoline derivatives, in human cancer cell lines.

Agents stabilizing G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalysed by telomerase or telomerase-independent mechanism and could therefore act as antitumor agents. In this study, we found that quindoline derivatives interacted preferentially with intramolecular G-quadruplex structures and were novel potent telomerase inhibitors. Treatment with quindoline derivatives reproducibly inhibited telomerase activity in human leukemia K562 cells and colon cancer SW620 cells. N'-(10H-Indolo [3,2-b] quinolin-11-yl)-N, N-dimethyl-propane-1,3-diamine (SYUIQ-5), (one of quindoline derivatives), when added to K562 and SW620 cell culture at nonacute cytotoxic concentrations, increased time of population doublings of K562 and SW620 cells, induced a marked cessation in cell growth and cellular senescence phenotype after 35 and 18 days, respectively. Growth cessation was accompanied by a shortening of telomere length, and induction of p16, p21 and p27 protein expression. However, another compound SYUIQ-7 with greater IC(50) for telomerase had no obvious cellular effect in nonacute cytotoxic concentrations. These results indicate that quindoline derivatives as novel potent G-quadruplex interactive agents induce senescence and telomere shortening in cancer cells and therefore are promising agents for cancer treatment.

Correlations between peripheral differential leukocyte counts and carotid atherosclerosis in non-smokers.

Substantial evidence clearly indicates the immuno-inflammatory nature of atherosclerosis and the important roles of monocytes and other leukocytes in atherogenesis. The relationship between atherosclerosis and the peripheral monocyte count, however, has been equivocal and uncertain so far. One possible reason may be an opposing effect of different major risk factors of atherosclerosis on the monocyte count, e.g. smoking increases the monocyte count while hypercholesterolemia is accompanied by a lower monocyte count. Since smoking is well shown to increase leukocyte counts prominently in weeks, our study included only non-smokers who participated in a health check program at our hospital from 1996 to 1998 and had received a carotid duplex study with extra payment. Our results revealed the followings: In male non-smokers (n=571), the presence of carotid atherosclerosis was associated with significant increases in the counts of all leukocyte, neutrophil, and monocyte (P<0.005,<0.001 and <0.05, respectively), and, after adjustments for age and body mass index, there were significant positive links between these three leukocyte counts and the severity of carotid atherosclerosis, judged by either the sum score of all carotid plaques or the score of the most severe carotid plaque. On the contrary, in female non-smokers (n=614), there was no significant link between differential leukocyte counts and either the presence or severity of carotid atherosclerosis. These results are compatible with recently recognized sex differences in the mechanism and pathophysiology of atherosclerosis, and together with relevant results in the literature, suggest that monocytes and neutrophils are the main types of leukocytes involved in atherosclerosis.

Peripheral differential leukocyte counts in humans vary with hyperlipidemia, smoking, and body mass index.

Reports of diverse relationships between blood concentrations of different lipids and peripheral total leukocyte count, and a unique lower peripheral monocyte count in hypercholesterolemia, have driven us to think that in humans, peripheral differential leukocyte counts may be influenced differently by different types of hyperlipidemia. Our subjects were Taipei residents who attended a regular health check program in our hospital in 1998. A total of 3,282 subjects was enrolled, including 1,677 normolipidemic, 960 untreated borderline hyperlipidemic, and 645 untreated hyperlipidemic subjects. By one-way analysis of variance (ANOVA), we found that different types of hyperlipidemia were associated with significant differences in differential leukocyte counts. In hypertriglyceridemia, the total leukocyte count and counts of all leukocyte subtypes were significantly higher than those in normolipidemia. Pure hypercholesterolemia, by contrast, was associated with a significantly lower monocyte count and no significant difference in other leukocyte counts. By two-way ANOVA adjusted for presence and degree of hyperlipidemia, we found significantly higher counts of total leukocytes and of all leukocyte subtypes in smokers, and significantly positive trends in relationships between body mass index (BMI) and counts of all leukocytes, neutrophils, lymphocytes, and monocytes. By multivariate regression analysis including all subjects, the serum triglyceride (TG) level was positively correlated with total leukocyte count and counts of all subtypes except eosinophils. On the contrary, serum high density lipoprotein-cholesterol had a negative correlation with total leukocyte count and with counts of neutrophils, monocytes, and basophils. In these multivariate regression analyses, there was no significant correlation between lipid levels and eosinophil count, whereas smoking was consistently associated with significantly higher counts of all leukocyte subtypes, including eosinophils. BMI had a significantly positive correlation with counts of all leukocytes, neutrophils, lymphocytes, and monocytes.

Serum level of soluble tumor necrosis factor receptor II (sTNF-R75) is apparently an index of overall monocyte-related infectious and inflammatory activity.

BACKGROUND: The serum level of soluble tumor necrosis factor receptor II (sTNF-R75) has been recently found to correlate with the activity and/or severity of several different infectious and inflammatory diseases. These results have led us to presume that the serum sTNF-R75 level reflects the active immune activity of all causes and may correlate well with nonspecific infectious and inflammatory markers such as peripheral leukocyte counts and serum C-reactive protein level. METHODS: In total, 110 apparently healthy adults, 55 men and 55 women, were enrolled in the study. Serum levels of sTNF-R75, C-reactive protein, globulin, alkaline phosphatase, lactate dehydrogenase, creatinine, urea nitrogen, and counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils were checked. The relationships between the serum sTNF-R75 level and other parameters were analyzed using the SAS statistical program. RESULTS: By various statistical methods, the serum sTNF-R75 level showed consistently significant positive links with peripheral monocyte count, serum C-reactive protein level, and two parameters of renal clearance function (serum urea nitrogen and creatinine levels). Serum levels of alkaline phosphatase and lactate dehydrogenase had significant positive links with the serum sTNF-R75 level by multivariate regression analysis. There was no significant link between the serum sTNF-R75 level and counts of neutrophils, lymphocytes, eosinophils, or basophils. CONCLUSIONS: Our results, together with those of recent reports showing positive correlations between the serum sTNF-R75 level and activities/severities of different infectious and inflammatory diseases, and also that TNF-alpha is principally produced by monocytes and macrophages, suggest that the serum sTNF-R75 level is very probably an index of overall monocyte-related infectious and inflammatory activities.

Identification and characterization of the RNA chaperone activity of hepatitis delta antigen peptides.

In this study, we identified an activity of the hepatitis delta antigen that both modulates the cis-cleaving activities of hepatitis delta virus (HDV) genomic RNA fragments and facilitates the trans-cleavage reactions between hammerhead ribozymes and the cognate substrates of various lengths in vitro. Hepatitis delta antigen peptides exert their effect by accelerating the unfolding and refolding of RNA molecules and by promoting strand annealing and strand dissociation. In addition, the stimulatory effect of hepatitis delta antigen peptide on hammerhead catalysis is observed whether the peptide is removed or not by phenol/chloroform extraction prior to the initiation of trans-cleavage reaction. Therefore, hepatitis delta antigen peptide acts as an RNA chaperone. The RNA chaperone domain of hepatitis delta antigen overlaps with the coiled-coil domain that is rich in lysine residues. The RNA binding domains of hepatitis delta antigen previously identified are not required for the RNA chaperone activity identified herein. The RNA chaperone activity of hepatitis delta antigen may be important for the regulation of HDV replication in vivo.