Monocytic myeloid-derived suppressor cells as an immune indicator of early diagnosis and prognosis in patients with sepsis.

BACKGROUND: Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. METHODS: LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. RESULTS: The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. CONCLUSIONS: MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

A Phase I Clinical Study of the Pharmacokinetics and Safety of Prusogliptin Tablets in Subjects with Mild to Moderate Hepatic Insufficiency and Normal Liver Function.

BACKGROUND: Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited. OBJECTIVES: The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment compared with healthy subjects. METHODS: According to the liver function of the subjects, we divided them into a mild liver dysfunction group, a moderate liver dysfunction group and a normal liver function group. All subjects in three groups received a single oral dose of Prusogliptin 100-mg tablets. Pharmacokinetics and safety index collection was carried out before and after taking the drug. Plasma pharmacokinetics of Prusogliptin were evaluated, and geometric least- -squares mean (GLSM) and associated 90% confidence intervals for insufficient groups versus the control group were calculated for plasma exposures. RESULTS: After a single oral administration of 100 mg of Prusogliptin tablets, the exposure level of Prusogliptin in subjects with mild liver dysfunction was slightly higher than that in healthy subjects. The exposure level of Prusogliptin was significantly increased in subjects with moderate liver dysfunction. There were no adverse events in this study. CONCLUSION: The exposure level of Prusogliptin in subjects with liver dysfunction was higher than that in healthy subjects. No participant was observed of adverse events. Prusogliptin tablets were safe and well tolerated in Chinese subjects with mild to moderate liver dysfunction and normal liver function.

Platelet activation is upregulated in cirrhotic patients with portal vein thrombosis.

OBJECTIVE: The alteration of platelet function plays a key role in thrombosis formation. This study aimed to explore platelet function alterations in the formation of portal vein thrombosis (PVT) in cirrhosis. METHODS: Cirrhotic patients admitted to hospital between October 2021 and April 2023 were recruited and divided into PVT and non-PVT groups. Flow cytometry was used to detect the expression of CD62p, CD63, monocyte-platelet aggregates (MPAs), neutrophil-platelet aggregates (NPAs) and vWF-Ag to evaluate platelet activation and adhesion function. RESULTS: A total of 145 subjects were enrolled in our study including 60 cirrhotic PVT patients, 60 cirrhotic non-PVT patients and 25 healthy volunteers. The expression of CD41+CD62p+ and CD41+CD63+ platelets in the PVT group was significantly elevated compared with that in the non-PVT group(P＜0.05). Subgroup analysis showed that the mean fluorescent intensity (MFI) of CD62p and CD63 was associated with portal hypertension-related complications (P＜0.05), and CD63 MFI was significantly associated with thrombosis burden (P=0.019). CD41+CD62p+ and CD41+CD63+ platelets as well as MPAs and NPAs were highly expressed in the splenectomy group (P＜0.05). Positive correlations were found between CD62p and CD63 MFI, MPAs and NPAs(P＜0.05). In addition, platelet counts were also correlated with MPAs (r=0.556, P＜0.001) and NPAs (r=0.467, P＜0.001). Cirrhotic patients with PVT had higher mortality and were more likely to experience portal hypertension-related complications (P＜0.05). CONCLUSION: Highly activated platelet function exists in patients with cirrhosis, and platelet activation was elevated during PVT formation, suggesting that activated platelets may participate in the formation of PVT in patients with cirrhosis.

Objective Evaluation of CT Imaging in the Treatment of Lumbar Disc Herniation.

The value of CT imaging in evaluating the efficacy of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of lumbar disc herniation (LDH) is explored. A total of 105 patients with LDH admitted to our hospital from March 2018 to September 2019 are selected for treatment with PTED, and all patients undergo CT examination before and after surgery. The CT imaging parameters (CT value of spinal canal soft tissue shadow, maximum back shift distance, longitudinal axis length, and intervertebral space height) before and 1 week after operation, the Japanese Orthopaedic Association (JOA) scores before and 6 months after the operation are compared, and the excellent and good rate of the operation effect is calculated. The correlation between JOA score and CT imaging parameters are analyzed by Pearson correlation method. The experimental results prove that PTED is effective in treating LDH. CT imaging can quantitatively measure the data of herniated intervertebral discs to clarify the recovery of the compressed dural sac and nerve roots, and the results are highly consistent with JOA score, which can be used as PTED objective evaluation method for the treatment of LDH.

Long non-coding RNA GAS5 contributes to the progression of nonalcoholic fatty liver disease by targeting the microRNA-29a-3p/NOTCH2 axis.

Long non-coding RNAs (lncRNAs) have been widely recognized as critical players in the development of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent liver diseases globally. In this study, we established a HFD-induced NAFLD mouse model and explored the role of lncRNA GAS5 in NAFLD progression and its possible underlying mechanisms. We showed that NAFLD activity score was elevated in the HFD mice. GAS5 knockdown attenuated HFD-induced hepatic steatosis and lipid accumulation and reduced NAFLD activity score in HFD mice. In addition, GAS5 knockdown reduced serum triglyceride cholesterol levels and inhibited alanine aminotransferase and aspartate aminotransferase activities in HFD mice. Moreover, GAS5 overexpression enhanced NOTCH2 levels in liver cells and promoted NAFLD progression by sponging miR-29a-3p in vivo. Furthermore, miR-29a-3p inhibited NAFLD progression by targeting NOTCH2 in vivo. Overall, our results indicated that GAS5 acts as a sponge of miR-29a-3p to increase NOTCH2 expression and facilitate NAFLD progression by targeting the miR-29a-3p/NOTCH2 axis and demonstrated a new GAS5-mediated mechanism underlying NAFLD development, suggesting that GAS5 could be a potential therapeutic target of NAFLD.Abbreviations: Alanine aminotransferase: ALT; Aspartate aminotransferase: AST; Enzyme linked immunosorbent assay: ELISA; Hepatocellular carcinoma: HCC; High-fat diet: HFD; Long non-coding RNA: Lnc RNA; Long non-coding RNA GAS5: GAS5; MicroRNAs: MiRNAs; Nonalcoholic fatty liver disease: NAFLD; Quantitative reverse transcription PCRs: RT-qPCRs; siRNA negative control: si-NC; Total cholesterol: TC; Triglyceride: TG.

Does the primary tumor site in stage I extranodal natural killer/T-cell lymphoma matter?

The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value. Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study. All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy. In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved. A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group). We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups. In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS. Multivariate analyses showed that the primary site (p=0.011) and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS. In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor. So, we think PCNI for stage I ENKTCL patients is not necessary. Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis. And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.

Clinical Evaluation and Therapeutic Effects of Combination Treatment with Mecobalamin + Vitamin E in Recurrent Oral Ulcer.

PURPOSE: Recurrent oral ulcer is one of the most prevalent inflammatory ulcerative disorders of the oral mucosa. Due to the indeterminant cause and unpredictable course of the disease, clinical treatment of patients with recurrent oral ulcer is focused on relieving the pain, shortening the course of the disease, and prolonging the intermission period. Numerous chemical and biologic agents have been characterized as beneficial in the treatment of patients with recurrent oral ulcer, but there is currently no definitive therapy available. This study aimed to investigate the clinical effects and tolerability of combined mecobalamin tablets and vitamin E capsules in the treatment of recurrent oral ulcer. METHODS: A total of 58 patients with recurrent oral ulcer admitted to our hospital were allocated to receive mecobalamin tablets + vitamin E soft capsules (test group) or Fe complex enzyme gargle only (control group) (n = 29 per group). Changes in parameters such as pain level, as measured on a 10-point visual analog scale (VAS); ulcer status and number of ulcers; proinflammatory cytokine levels; and quality of life, as measured using SF-36, from before to after treatment were measured. Mean intermission time and mean ulcer healing time were calculated. Total effectiveness rate was also calculated. The occurrences of adverse reactions in the two groups were quantified. FINDINGS: The total intermission time interval was significantly longer, the mean ulcer healing time was considerably shorter, the total number of ulcers was appreciably less, and the total effectiveness rate was significantly greater in the test group compared to the control group (all, P < 0.05). The VAS scores were significantly greater after treatment than before treatment in both the test and control groups (mecobalamin + vitamin E, 2.16 [1.09] vs 7.87 [0.51]; control, 3.72 [1.15] vs 7.94 [0.56]; both, P < 0.05). Interleukin (IL)-8, tumor necrosis factor α, and C-reactive protein levels were appreciably down-regulated in both groups when compared to before treatment. In addition, IL-2 concentration and SF-36 scores were much greater after treatment in the test group with respect to the control group. Levels of IL-8, TNF-α, and CRP were significantly lesser in the test group than in the control group (all, P < 0.05). IMPLICATIONS: The combination of mecobalamin tablets and vitamin E soft capsules was effective in the treatment of recurrent oral ulcer. This combination can be used as an adjunctive therapy, offering effective pain control and improving quality of life in patients with oral ulcers.

Autophagy deficiency promotes M1 macrophage polarization to exacerbate acute liver injury via ATG5 repression during aging.

Aging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute liver injury (ALI), ultimately leading to the development of acute liver failure (ALF), a systemic inflammatory response, and even death. Macrophages influence the progression and outcome of ALI through the innate immune system. However, it is still unclear how macrophages regulate ALI during aging. The variation in macrophage autophagy with aging and the influence on macrophage polarization and cytokine release were assessed in BMDMs in vitro. Then, after BMDMs subjected to several treatments were intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced ALI (TAA-ALI) was established, and its effects on inflammation, injury, and mortality were assessed. We found that aging aggravated the liver injury, along with increases in the levels of proinflammatory mediators, presenting a senescence-associated secretory phenotype (SASP), which promoted macrophage polarization to the M1 phenotype. In addition, autophagy levels decreased significantly in aged mice, which was ascribed to ATG5 repression during aging. Notably, enhancing autophagy levels in aged BMDMs restored macrophage polarization to that observed under young conditions. Finally, autophagy restoration in aged BMDMs enhanced the protective effect against TAA-ALI, similar to M2 macrophages induced by IL-4. Overall, we demonstrated that the influence of aging on macrophage polarization is an important aggravating factor in TAA-ALI, and the autophagy in macrophages is associated with the aging phenotype.

ZNRD1-AS1 knockdown alleviates malignant phenotype of retinoblastoma through miR-128-3p/BMI1 axis.

BACKGROUND: ZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been studied in detail. This study aimed to determine the role of ZNRD1-AS1 in retinoblastoma. METHODS: Differentially expressed genes in retinoblastoma downloaded from GEO database were identified by Limma package, and the expression and cell location of ZNRD1-AS1 were detected by real-time quantitative PCR (RT-qPCR). The relationships between miR-128-3p and two genes (ZNRD1-AS1 and BMI1) were analyzed by bioinformatics and dual-luciferase assay. After manipulating the expressions of ZNRD1-AS1, miR-128-3p and BMI1, cell viability, tube length, migration, invasion and the protein expressions (PCNA, E-Cadherin, N-Cadherin) of retinoblastoma cells were determined by cell counting kit-8 (CCK-8), tube formation, transwell and Western blot assays, respectively. Subcutaneous transplantation tumor assay, immunohistochemistry, and RT-qPCR were applied to verify the functions of the target gene in vivo. RESULTS: ZNRD1-AS1 was up-regulated in the cytoplasm of retinoblastoma and regulated BMI1 via sponging miR-128-3p. ZNRD1-AS1 knockdown alleviated the malignant phenotype (viability, tube length, migration and invasion) of retinoblastoma cells, reduced tumor volume and weight, and inhibited BMI1 and CD34 expressions. Different from miR-128-3p mimic, miR-128-3p inhibitor promoted malignant phenotype of retinoblastoma cells, and partially reversed the inhibitory effect of siZNRD1-AS1. MiR-128-3p mimic down-regulated BMI1, PNCA, N-Cadherin expressions, and up-regulated p16 and E-Cadherin expressions. The regulatory effect of miR-128-3p was partially reversed by BMI1. CONCLUSION: ZNRD1-AS1, acting as a "sponge" of miR-128-3p, up-regulates BMI1, thereby promoting the progression of retinoblastoma.

Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review).

External and internal stimuli are often involved in the pathogenesis of tumors, and the deterioration of endoplasmic reticulum (ER) function within cells is also an important etiological factor of tumorigenesis resulting in the impairment of the endoplasmic reticulum, which is termed ER stress. The ER is an organelle that serves a crucial role in the process of protein synthesis and maturation, and also acts as a reservoir of calcium to maintain intracellular Ca2+ homeostasis. ER stress has been revealed to serve a critical role in tumorigenesis. In the present review, the association between ER stress­related pathways and tumor cell apoptosis is examined. Primarily, the role of ER stress in tumor cell apoptosis is discussed, and it is stipulated that ER stress, induced by drugs both directly and indirectly, promotes tumor cell apoptosis.

Nitroglycerin ameliorates liver injury and regulates adaptive immunity in mice.

This study aimed to assess the protective effect of nitroglycerin, a commonly used drug in cardiovascular diseases, on mice with acute liver injury induced by carbon tetrachloride (CCl4 ). The mice were randomly divided into three groups: control, CCl4 , and CCl4 + nitroglycerin. They were killed at 0, 6, 12, 24, and 48 h after treatment. Blood and liver tissue samples were collected for analysis. Analysis of the amounts of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hepatic glutathione (GSH), and malondialdehyde (MDA) showed that nitroglycerin protected against CCl4 -induced acute liver injury. Liver histological analysis provided further evidence of the protective effect of nitroglycerin. Furthermore, we found that nitroglycerin suppressed the increase of T helper 17 (Th17) cells in CCl4 -induced acute liver injury mice. The results indicate that nitroglycerin is a potential candidate for hepatic disease.

Nuclear-localized costimulatory molecule 4-1BBL promotes colon cancer cell proliferation and migration by regulating nuclear Gsk3ß, and is linked to the poor outcomes associated with colon cancer.

Anti-tumor immune response and the prognosis of tumor are the results of competition between stimulatory and inhibitory checkpoints. Except for upregulating inhibitory checkpoints, lowering some immune accelerating molecules to convert an immunostimulatory microenvironment into an immunodormant one through "decelerating the accelerator" might be another effective immune escape pattern. 4-1BBL is a classical transmembrane costimulatory molecule involving in antitumor immune responses. In contrast, we demonstrated that 4-1BBL is predominantly localized in the nuclei of cancer cells in colon cancer specimens and is positively correlated with tumor size, lymph node metastasis, and a lower survival ratio. Furthermore, the nuclear localization of 4-1BBL was also ascertained in vitro. 4-1BBL knockout (KO) arrests the proliferation and impaired the migration and invasion ability of colon cancer cells in vitro and retarded tumor growth in vivo. 4-1BBL KO increased the accumulation of Gsk3ß in the nuclei of colon cancer cells and consequently decreased the expression of Wnt pathway target genes and thus alter tumor biological behavior. We hypothesized that unlike membrane-expressed 4-1BBL, which stimulates the 4-1BB signaling of antitumor cytotoxic T cells, the nuclear-localized 4-1BBL could facilitate the malignant behavior of colon cancer cells by circumventing antitumor signaling and driving some key oncotropic signal pathway in the nucleus. Nuclear-localized 4-1BBL might be an indicator of colon cancer malignancy and serve as a promising target of immunotherapy.

Arterial stiffness in adults with steady-state bronchiectasis: association with clinical indices and disease severity.

BACKGROUND: Cardiovascular disease are common co-morbidities in bronchiectasis and contribute substantially to disease burden and mortality. Brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, has a strong predictive value for cardiovascular event. We hypothesized that baPWV would be increased in steady-state bronchiectasis patients, and correlates with the degree of systemic inflammation and disease severity assessed with Bronchiectasis Severity Index and FACED scores. METHODS: Eighty patients with steady-state bronchiectasis and 80 age- and sex-matched controls were enrolled. BaPWV was measured as an indicator of arterial stiffness. Demographic, clinical indices, radiology, spirometry, sputum bacteriology and systemic inflammatory mediators were also assessed. RESULTS: Bronchiectasis patients had significantly increased baPWV [median 1514 cm/s vs. 1352 cm/s, P = 0.0003] compared with control subjects. BaPWV significantly correlated with Bronchiectasis Severity Index (rho = 0.65, P < 0.001) and FACED (rho = 0.49, P < 0.001) scores. In multivariate regression analysis, age, Pseudomonas aeruginosa colonization, systolic blood pressure, body-mass index and exacerbation frequency in the last 12 months, but not systemic inflammatory markers, were independent factors influencing on baPWV in bronchiectasis patient after adjustment for other clinical variables. Reproducibility of baPWV measurement was good. CONCLUSION: Bronchiectasis patients have increased arterial stiffness compared with control subjects, which correlates with disease severity, but not systemic inflammatory markers. Age, Pseudomonas aeruginosa colonization, systolic blood pressure, body-mass index and exacerbation frequency in last 12 months might independently predict the severity of arterial stiffness in bronchiectasis. Therefore, arterial stiffness might have contributed to the increased risks of developing cardiovascular diseases in bronchiectasis.

Subclinical atherosclerosis in adults with steady-state bronchiectasis: A case-control study.

BACKGROUND AND OBJECTIVE: Bronchiectasis has been associated with increased risks of cardiovascular disease, in which early-stage endothelial dysfunction might have played pivotal roles. We aimed to investigate endothelial function in bronchiectasis patients, by measuring flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT) as compared with control subjects, and to elucidate the impact of different risk factors on subclinical atherosclerosis. METHODS: The study included 80 bronchiectasis patients and 80 age- and sex-matched healthy subjects. Vascular endothelial function was evaluated with FMD in the brachial artery in response to reactive hyperemia, and CIMT was measured with high-resolution ultrasonography. Disease severity was evaluated with Bronchiectasis Severity Index and FACED scores. Demographic, disease duration, radiology, spirometry, sputum bacteriology and systemic inflammatory indices were also assessed. RESULTS: FMD was significantly lower in bronchiectasis patients than in control subjects (8.92 ± 2.70% vs. 11.17 ± 3.44%, P < 0.001). FMD significantly correlated with Bronchiectasis Severity Index (rho = -0.60, P < 0.001) and FACED score (rho = -0.39, P < 0.001). In multivariate regression analysis, age, body-mass index, Pseudomonas aeruginosa colonization and high-resolution computed tomography scores were independent factors influencing on the FMD in bronchiectasis patients, even after adjustment for other clinical variables. No significant difference in CIMT was detected between bronchiectasis patients and healthy subjects (P > 0.05). CONCLUSIONS: Compared with healthy subjects, bronchiectasis patients have greater risks of endothelial dysfunction which is independent of previously well-studied risk factors, calling for the vigilance to screen early for vascular changes to minimize the future risks of cardiovascular events.

Protective efficacy of inhaled quercetin for radiation pneumonitis.

Radiation pneumonitis is a clinical problem with a high incidence. Once the onset of radiation pneumonitis has occurred, the administration of antioxidants and anti-inflammatory agents is the most commonly used method of clinical treatment. Quercetin (Que) is a common flavonoid, with potent anti-inflammatory and anti-oxidant activities. In the present study, the therapeutic effect of inhaled Que on radiation-induced radiation pneumonitis in rats was investigated. Treatment with Que via inhalation was shown to increase the number of leukocytes and erythrocytes in the blood, and reduce the number of inflammatory cells in bronchoalveolar lavage fluid. Histological examination of lung tissue indicated that inhaled Que reduced hemorrhaging and the infiltration of inflammatory cells, and suppressed the expression of the proinflammatory cytokines transforming growth factor-ß1 and interleukin-6. These results indicated that treatment with Que via inhalation ameliorates radiation pneumonitis by reducing the number of inflammatory cells, and attenuating the inflammatory response and pathological changes. This suggests that administration of Que via inhalation has the potential to become a novel treatment for radiation pneumonitis.

Subclinical atherosclerosis risk markers in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Identifying early changes of cardiovascular system before the occurrence of fatal clinical event is critical for the management of COPD. We performed a meta-analysis to investigate the associations between COPD and subclinical markers of cardiovascular risk. METHODS: We searched PUBMED, EMBASE for studies published before Aug 1st, 2016, on the association between COPD and carotid intima-media thickness (CIMT), prevalence of carotid plaques, flow-mediated dilation (FMD), pulse-wave velocity (PWV) and augmentation index (AIx). RESULTS: Thirty-two studies (3198 patients, 13867 controls) were included. Compared with controls, COPD patients had significantly higher CIMT (MD: 0.10 mm; 95% CI: 0.04, 0.16; p = 0.0007), PWV (SMD: 0.70; 95% CI: 0.52, 0.88; p < 0.0001), AIx (MD: 4.60%; 95% CI: 0.52, 8.68; p = 0.03), AIx@75 (AIx normalized to a heart rate of 75 beats per minute) (MD: 4.59%; 95% CI: 2.80, 6.38; p < 0.0001), prevalence of carotid plaque (OR: 2.54; 95% CI: 2.04, 3.15; p < 0.0001), and significantly lower FMD (MD: -4.21%; 95% CI: -6.71, -1.71; p = 0.001). Sensitivity and subgroups analyses substantially confirmed our results. Meta-regression analysis revealed that spirometry (as expressed by FEV1%predicted) might influence on PWV. CONCLUSIONS: These findings indicate that COPD, even in mild to moderate patients, had greater impaired markers of subclinical atherosclerosis and cardiovascular risk. However, further studies are still needed to address confounders, such as age, smoking, hypertension, diabetes etc, which might affect the associations in COPD patients.

Aetiology of bronchiectasis in adults: A systematic literature review.

While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management remain unclear. We aimed to determine the etiological spectrum of bronchiectasis, and how often etiological assessment could lead to the changes in patients' management. A comprehensive search was conducted using MEDLINE (via PubMed) and EMBASE for observational studies published before October 2015 reporting aetiologies in adults with bronchiectasis. Of the 8216 citations identified, 56 studies including 8608 adults with bronchiectasis were relevant for this systematic review. The crude prevalence for the identified aetiologies ranged from 18% to 95%, which possibly resulted from the differences in the geographic regions and diagnostic workup. Post-infective (29.9%), immunodeficiency (5%), chronic obstructive pulmonary disease (3.9%), connective tissue disease (3.8%), ciliary dysfunction (2.5%), allergic bronchopulmonary aspergillosis (2.6%) were the most common aetiologies. In 1577 patients (18.3%), identifying the aetiologies led to changes in patient's management. Aetiologies varied considerably among different geographic regions (P < 0.001). Intensive investigations of these aetiologies might help change patient's management and therefore should be incorporated into routine clinical practice.

[Mining and characterization of miRNAs closely associated with the pathogenicity in tomato].

MicroRNAs (miRNAs) are a class of small endogenously RNA with an approximate length of 22nt which are known to be ubiquitous in eukaryotes. More importantly, miRNAs are key regulators of gene expression in eukaryotic cells through the degradation of target mRNA. The investigation on miRNAs in tomato that is an important model plant has made a great progress in recent years. Herein, by collecting the reported literature and miRBase, we found that 34 miRNAs in tomato are closely associated with pathogenicity. Subsequently, we predicted their target genes through bioinformatics approaches and built a disease-related regulatory network of miRNA and its target genes using Cytoscope program. This has led us to identify 13 miRNAs that are closely associated with pathogenicity in tomato from which we selected miR169, miR482, miR5300, miR6024, miR6026 and miR6027 for further analysis based on the association between miRNAs and the number of target genes. Lastly, we performed the analysis of target gene, promoter and real time quantitative PCR verification for these 6 miRNAs. Our study may pave the way for future in-depth analysis of biological action of miRNAs.

Prediction and validation of potential pathogenic microRNAs involved in Phytophthora infestans infection.

Being one kind of approximately 22nt long small RNA, miRNA has shown its roles in host-pathogen interaction, providing one possible way for pathogen infection. Though Phytophthora infestans is a major pathogen that causes devastating late blight of potato, tomato and so on, so far there have not been any systematic researches on miRNAs and even pathogenic miRNAs in P. infestans. Here, for the first time we comprehensively predicted and identified pathogenic miRNAs that may exist in P. infestans. First, a total of 128 putative miRNAs belonging to 66 miRNA family were identified by bioinformatic approaches. Then, 33 vital pathogenic miRNAs were screened by constructing miRNA-miRNA relationship networks. Finally, four potential pathogenic miRNAs were chosen for detection, two of which are chosen for validation. The expression quantity of pi-miR466 and pi-miR1918 changed dramatically during incubation of tomato leaves, implying that they are potential pathogenic miRNAs.